2024 |
Shafiei M, Galettis P, Beale P, Martin JH, McLachlan AJ, Blinman P, 'Comparison of capecitabine concentrations determined by microsampling versus plasma concentrations for therapeutic drug monitoring: a pilot study.', J Pharm Pharmacol, 76 86-92 (2024) [C1]
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Nova |
2024 |
Erku D, Martin JH, Michael M, Galettis P, Scuffham P, 'Economic evaluation of personalized vs. standard dosing of 5-fluorouracil in first-line chemotherapy for metastatic colorectal cancer in Australia.', Br J Clin Pharmacol, (2024) [C1]
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2024 |
Martin JH, Galettis P, Flynn A, Schneider J, 'Phenotype versus genotype to optimize cancer dosing in the clinical setting-focus on 5-fluorouracil and tyrosine kinase inhibitors.', Pharmacol Res Perspect, 12 e1182 (2024) [C1]
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2024 |
Radovanovic M, Galettis P, Flynn A, Martin JH, Schneider JJ, 'Paclitaxel and Therapeutic Drug Monitoring with Microsampling in Clinical Practice', Pharmaceuticals, 17 (2024) [C1]
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Nova |
2023 |
Shafiei M, Mahmood A, Beale P, Galettis P, Martin J, McLachlan AJ, Blinman P, 'Dried Blood Spot Sampling in the Monitoring of Anticancer Therapy for Solid Tumors: A Systematic Review.', Therapeutic drug monitoring, 45 293-305 (2023) [C1]
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Nova |
2023 |
Milliken E, Galettis P, Martin J, 'A review of psilocybin: chemistry, clinical uses and future research directions', AUSTRALIAN JOURNAL OF CHEMISTRY, 76 258-263 (2023) [C1]
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Nova |
2023 |
Tong Z, Esser L, Galettis P, Rudd D, Easton CD, Nilghaz A, et al., 'Fluoropolymer Functionalization of Organ-on-Chip Platform Increases Detection Sensitivity for Cannabinoids', Biosensors, 13 779-779 [C1]
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Nova |
2023 |
Shafiei M, Galettis P, Beale P, Reuter SE, Martin JH, McLachlan AJ, Blinman P, 'Influence of age on pharmacokinetics of capecitabine and its metabolites in older adults with cancer: a pilot study', Cancer Chemotherapy and Pharmacology, 92 135-139 (2023) [C1]
Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate th... [more]
Background: Capecitabine is an oral chemotherapy prodrug of 5-fluorouracil (5-FU) with unpredictable toxicity, especially in older adults. The aim of this study was to evaluate the pharmacokinetics (PK) of capecitabine and its metabolites in younger adults (< 70¿years) and older adults (= 70¿years) receiving capecitabine for solid cancer. Methods: Eligible participants receiving capecitabine had 2 venous samples collected on day 14 of cycle 1 and cycle 2 of their treatment. Capecitabine and metabolite concentrations were determined using liquid chromatography with tandem mass spectrometry. A Bayesian estimation approach was used to generate individual estimates of PK parameters for 5-FU. A linear mixed-effect analysis of variance (ANOVA) model was used to compare dose-normalised log-transformed PK parameters between age groups. Correlations were determined by linear regression and logistic regression analyses. Results: Of the total 26 participants, 58% were male with a median age of 67¿years (range, 37¿85) with 54% aged < 70¿years and 46% aged = 70¿years. Participants aged = 70¿years, compared to those aged < 70¿years, had a greater 5-FU exposure based on area under the concentration¿time curve (AUC) of 17% (90% CI 103¿134%; 0.893 vs. 0.762¿mg h/L) and 14% increase in maximal concentration, Cmax (90% CI 82.1¿159%; 0.343 vs. 0.300¿mg/L). The 5-FU Cmax was positively associated with time up and go (TUG) (Pearson¿s correlation 0.77, p = 0.01), but not other geriatric assessment domains or severe toxicity. Conclusion: 5-FU exposure was significantly increased in older adults compared to younger adults receiving equivalent doses of capecitabine, and is a possible cause for increased toxicity in older adults.
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2023 |
Lorenzetti V, McTavish E, Broyd S, van Hell H, Thomson D, Ganella E, et al., 'Daily Cannabidiol Administration for 10 Weeks Modulates Hippocampal and Amygdalar Resting-State Functional Connectivity in Cannabis Users: A Functional Magnetic Resonance Imaging Open-Label Clinical Trial.', Cannabis Cannabinoid Res, (2023) [C1]
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2023 |
Jake Shortt, Galettis P, Cheah CY, Davis J, Ludford-Menting M, Link EK, et al., 'A phase 1 clinical trial of the repurposable acetyllysine mimetic, n-methyl-2-pyrrolidone (NMP), in relapsed or refractory multiple myeloma', Clinical Epigenetics, 15 (2023) [C1]
Background: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Pre... [more]
Background: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR¿MM). Secondary endpoints were safety, pharmacokinetics (PK), overall response rate and immunological biomarkers of activity. Results: Thirteen patients received NMP at starting doses between 50 and 400¿mg daily. Intra-patient dose escalation occurred in five patients, with one attaining the ceiling protocolised dose of 1¿g daily. Median number of monthly cycles commenced was three (range 1¿20). Grade 3¿4 adverse events (AEs) were reported in seven (54%; 95% CI 25¿81%) patients. Most common AEs (> 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200¿mg NMP (overall DLT rate 8%; 95% CI 0¿36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29¿539) days and 33 (95% CI 9.7¿ > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39¿91%). PK analysis demonstrated proportional dose¿concentrations up to 400¿mg daily, with a more linear relationship above 500¿mg. Maximum plasma concentrations (Cmax) of 16.7¿mg/L at the 800¿mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12¿months. Conclusions: NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR¿MM; an MTD was not determined up to a maximum dose of 1¿g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.
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Nova |
2022 |
Radovanovic M, Jones G, Day RO, Galettis P, Norris RLG, 'Mitigating analyte to stable isotope labelled internal standard cross-signal contribution in quantitative liquid chromatography-tandem mass spectrometry', Journal of Mass Spectrometry and Advances in the Clinical Lab, 24 57-64 (2022) [C1]
Background: Utilising stable isotope labelled internal standards (SIL-IS) in quantitative LC-MS/MS drug analysis is the most widely used approach to normalise for variability duri... [more]
Background: Utilising stable isotope labelled internal standards (SIL-IS) in quantitative LC-MS/MS drug analysis is the most widely used approach to normalise for variability during sample quantification processes. However, compounds containing atoms such as Sulphur, Chlorine or Bromine, could potentially cause cross-signal contribution to the SIL-IS from the naturally occurring isotopes, resulting in non-linear calibration curves. A simple, novel method of mitigating the effect is presented here. It entails monitoring of a less abundant SIL-IS isotope, as the precursor ion, of a mass that has no/minimal isotopic contribution from the analyte isotopes. Methods: Experiments were conducted on two LC-MS/MS analysers: Waters Xevo TQ-S and Shimadzu 8050. Flucloxacillin (FLX) was used as an example. Two transitions were selected for FLX (m/z 454 ¿ 160 ¿ 295) and one for each of the SIL-IS isotopes (m/z 458 ¿ 160 for the isotope 457 g/mol and m/z 460 ¿ 160 for the isotope 459 g/mol). Assay biases were assessed at three SIL-IS concentrations: 0.7, 7 and 14 mg/L for each isotope. Results: When using the SIL-IS isotope m/z 458 ¿ 160 at a concentration of 0.7 mg/L, biases were up to 36.9 % on both instruments. Increasing the SIL-IS concentration to 14 mg/L, reduced the bias to 5.8 %. Using the less abundant isotope, m/z 460 ¿ 160, resulted in biases of 13.9 % at an SIL-IS concentration of 0.7 mg/L. Conclusions: Applying this method will mitigate cross-signal contribution from the analyte isotopes to the corresponding SIL-IS, minimise the use of SIL-IS, and, thereby, reduce overall cost.
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Nova |
2022 |
Hurley EN, Ellaway CJ, Johnson AM, Truong L, Gordon R, Galettis P, et al., 'Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial', EPILEPSIA, 63 1736-1747 (2022) [C1]
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Nova |
2022 |
Bonomo Y, Norman A, Collins L, O Neill H, Galettis P, Trinca J, et al., 'Pharmacokinetics, Safety, and Tolerability of a Medicinal Cannabis Formulation in Patients with Chronic Non-cancer Pain on Long-Term High Dose Opioid Analgesia: A Pilot Study', Pain and Therapy, 11 171-189 (2022) [C1]
Introduction: This phase¿I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydroca... [more]
Introduction: This phase¿I open-label study examined pharmacokinetics, safety, and tolerability of escalating doses of a novel combination cannabinoid medication (1:1 tetrahydrocannabinol [THC]/cannabidiol [CBD]) in patients with chronic non-cancer pain (CNCP) on high dose opioid analgesia. Methods: Nine people with CNCP and oral morphine equivalent daily dose of 60¿mg or higher were recruited. Blood concentrations of THC, 11-hydroxytetrahydrocannabinol (OH-THC), 11-nor-9-carboxy-tetrahydrocannabinol (COOH-THC), and CBD were assayed weekly. Concentrations were measured after a single dose of 2.5¿mg THC/2.5¿mg CBD on day¿1, and daily escalating doses up to a single dose of 12.5¿mg THC/12.5¿mg CBD on day¿29. Follow-up was on day¿36 after a 7-day washout. Secondary outcome data encompassed pain, mood, and sleep parameters. Results: The parent compounds THC, and CBD, and metabolites OH-THC and COOH-THC were detected at most time points. In general, the concentration of all analytes increased until 2¿h post-administration, decreasing to approximately pre-dose concentrations by 8¿h. There was considerable inter- and intra-individual variability. The study medication was well tolerated. Eight participants reported at least one adverse event (AE), with a total of 62 AEs; most common were euphoric mood, headache, and agitation, none classified as severe. There was no significant change to pain severity self-ratings, nor use of pain medications. Improvements in pain interference scores, mood, and some sleep parameters were observed. Conclusion: The THC/CBD formulation was tolerated well in a group of patients with CNCP. Between-participant variability supports personalized dosing and ¿start low¿go slow¿ titration. To validate and quantify improvements in secondary efficacy outcomes a randomized placebo-controlled study is needed. Trial Registration: Australian New Zealand Clinical Trials Register (CT-2019-CTN-01224-1).
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Nova |
2022 |
Radovanovic M, Day RO, Jones GDR, Galettis P, Norris RLG, 'LC-MS/MS method for simultaneous quantification of ten antibiotics in human plasma for routine therapeutic drug monitoring', JOURNAL OF MASS SPECTROMETRY AND ADVANCES IN THE CLINICAL LAB, 26 48-59 (2022) [C1]
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Nova |
2022 |
Radovanovic M, Schneider JJ, Shafiei M, Martin JH, Galettis P, 'Measurement of 5- fluorouracil, capecitabine and its metabolite concentrations in blood using volumetric absorptive microsampling technology and LC-MS/MS', Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1188 (2022) [C1]
5-fluorouracil (5-FU) and its oral formulation, capecitabine, are widely used in treating a range of malignancies, either alone or in combination with other antineoplastic drugs. ... [more]
5-fluorouracil (5-FU) and its oral formulation, capecitabine, are widely used in treating a range of malignancies, either alone or in combination with other antineoplastic drugs. Body surface area-based dosing is used for these agents, despite this approach leading to substantial variability in drug exposure and often resulting in either toxicity or treatment failure. Tailoring therapeutic regimens for individual patients using therapeutic drug monitoring (TDM) has been shown to significantly reduce toxicity and improve cancer outcomes. However, for optimum TDM, sample timing is crucial, along with the need for a venepuncture blood sample to obtain the plasma currently used for 5-FU measurement. In addition to complex blood sample handling requirements, large sample volume and frequent sampling required for pharmacokinetic analysis is another barrier to successfully implementing TDM in a healthcare setting. Microsampling is an alternative collection method to venepuncture, which, combined with the now readily available liquid chromatography mass spectrometry (LC-MS/MS) technology, overcomes the plasma-associated issues. It also has the significant advantage of enabling at home and remote sampling, thus facilitating 5-FU TDM in clinical practice. A LC-MS/MS method for simultaneous measurement of capecitabine, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-FU using Mitra® microsampling devices for sample collection was developed. A Shimadzu 8060 LC-MS/MS equipped with electrospray ionisation source interface, operated in positive and negative ion modes, with reversed-phase chromatographic separation was employed for sample analysis. Samples were extracted from Mitra® devices using acetonitrile containing stable isotope-labelled internal standards, sonicated, evaporated under vacuum and resuspended in 0.1 % formic acid before injection into the LC-MS/MS. Chromatographic separation was on a Luna Omega Polar C18 (100 × 2.1 mm, 1.6 µm) column with gradient elution of 0.1 % formic acid in water and acetonitrile. Total run time was 5 min, with the injection volume of 1 µL. The intra and inter-day imprecision ranged from 3.0 to 8.1 and 6.3¿13.3 % respectively. Accuracy ranged from 95 -114 % for all analytes. Lower limit of quantification with imprecision of < 19 % and accuracy between 89 and 114 % was 0.05 mg/L for 5-FU and 10 µg/L for other analytes. Assays were linear from 0.05 to 50 mg/L for 5-FU and 10¿10,000 µg/L for all other analytes. Analytes were stable on Mitra® devices for up to 9 months at room temperature, 2 years at -30 ¿ and 3 days at 50 ¿. The method was successfully applied for the analysis of samples from patients undergoing cancer treatment with 5-FU and capecitabine. Microsampling using volumetric absorptive microsampling proved to be as reliable as conventional blood collection for 5-FU and capecitabine. This sampling technique may lead to less invasive and better-timed sample collection for TDM, supporting dose optimization strategy.
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Nova |
2021 |
Menz BD, Stocker SL, Verougstraete N, Kocic D, Galettis P, Stove CP, Reuter SE, 'Barriers and opportunities for the clinical implementation of therapeutic drug monitoring in oncology', British Journal of Clinical Pharmacology, 87 227-236 (2021) [C1]
There are few fields of medicine in which the individualisation of medicines is more important than in the area of oncology. Under-dosing can have significant ramifications due to... [more]
There are few fields of medicine in which the individualisation of medicines is more important than in the area of oncology. Under-dosing can have significant ramifications due to the potential for therapeutic failure and cancer progression; by contrast, over-dosing may lead to severe treatment-limiting side effects, such as agranulocytosis and neutropenia. Both circumstances lead to poor patient prognosis and contribute to the high mortality rates still seen in oncology. The concept of dose individualisation tailors dosing for each individual patient to ensure optimal drug exposure and best clinical outcomes. While the value of this strategy is well recognised, it has seen little translation to clinical application. However, it is important to recognise that the clinical setting of oncology is unlike that for which therapeutic drug monitoring (TDM) is currently the cornerstone of therapy (e.g. antimicrobials). Whilst there is much to learn from these established TDM settings, the challenges presented in the treatment of cancer must be considered to ensure the implementation of TDM in clinical practice. Recent advancements in a range of scientific disciplines have the capacity to address the current system limitations and significantly enhance the use of anticancer medicines to improve patient health. This review examines opportunities presented by these innovative scientific methodologies, specifically sampling strategies, bioanalytics and dosing decision support, to enable optimal practice and facilitate the clinical implementation of TDM in oncology.
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Nova |
2021 |
Campbell EJ, Bonomo Y, Pastor A, Collins L, Norman A, Galettis P, et al., 'The 5-HT
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Nova |
2021 |
Galettis P, Williams M, Gordon R, Martin JH, 'A Simple Isocratic HPLC Method for the Quantitation of 17 Cannabinoids', AUSTRALIAN JOURNAL OF CHEMISTRY, 74 453-462 (2021) [C1]
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Nova |
2021 |
Schneider JJ, Galettis P, Martin JH, 'Overcoming barriers to implementing precision dosing with 5-fluorouracil and capecitabine', BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 87 317-325 (2021) [C1]
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Nova |
2021 |
Majimbi M, Brook E, Galettis P, Eden E, Al-Salami H, Mooranian A, et al., 'Sodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid', PLOS ONE, 16 (2021) [C1]
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Nova |
2020 |
Teng C, Reuter SE, Blinman PL, Dhillon HM, Galettis P, Proschogo N, et al., 'Ibudilast for prevention of oxaliplatin-induced acute neurotoxicity: a pilot study assessing preliminary efficacy, tolerability and pharmacokinetic interactions in patients with metastatic gastrointestinal cancer', Cancer Chemotherapy and Pharmacology, 86 547-558 (2020) [C1]
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Nova |
2020 |
Harris BDW, Phan V, Perera V, Szyc A, Galettis P, Martin JH, et al., 'Inability of Current Dosing to Achieve Carboplatin Therapeutic Targets in People with Advanced Non-Small Cell Lung Cancer: Impact of Systemic Inflammation on Carboplatin Exposure and Clinical Outcomes', Clinical Pharmacokinetics, 59 1013-1026 (2020) [C1]
Background: The presence of elevated systemic inflammation in people with advanced non-small cell lung cancer (NSCLC) is associated with significantly shorter survival following c... [more]
Background: The presence of elevated systemic inflammation in people with advanced non-small cell lung cancer (NSCLC) is associated with significantly shorter survival following carboplatin-based chemotherapy. Objective: This study investigated whether novel factors, such as systemic inflammation [platelet¿lymphocyte ratio (PLR) and neutrophil¿lymphocyte ratio (NLR)], impact carboplatin pharmacokinetics and drug utilisation. The study also examined the ability of current and alternate dosing regimens to meet therapeutic targets. Methods: Seventy-two people with advanced NSCLC treated with carboplatin-based (460¿1050 mg) doublet chemotherapy were recruited and pharmacokinetic data (n = 61) were analysed using non-linear mixed modelling. Covariate analysis was performed to investigate the impact of standard and novel patient characteristics of carboplatin pharmacokinetics. A Monte Carlo simulation of 100,000 representative NSCLC patients evaluated the ability of the Calvert formula and novel dosing strategies to achieve the targeted therapeutic range. The associations between systemic inflammation and chemotherapy drug utilisation (cycles received, relative dose intensity (RDI) and second-line uptake) and clinical endpoints were also investigated in the pharmacokinetic cohort, and two independent cohorts of people with advanced NSCLC from the Chemotherapy Dosing in Cancer-Related Inflammation (CDCRI) database¿that were administered carboplatin¿paclitaxel (n = 37) or carboplatin¿gemcitabine (n = 358). Results: In all cohorts, 25¿53% of people had elevated systemic inflammation (NLR > 5 or PLR > 300). In the pharmacokinetic cohort, no patients achieved the desired therapeutic target of carboplatin. Carboplatin exposure was related to renal function, as estimated using the Cockcroft¿Gault formula, albumin and inflammation (NLR). In the pharmacokinetic cohort, increasing carboplatin area under the curve (AUC) correlated with greater reductions in red blood cells and haemoglobin. In this cohort, the average measured AUC of partial responders was 2.4¿mg·min/mL. Also in the pharmacokinetic cohort, only 12% of people with an NLR > 5 received four or more cycles of chemotherapy, compared with 62% of patients with an NLR = 5 (p < 0.001). For people in the CDCRI cohort receiving carboplatin¿gemcitabine, those with an NLR > 5 also received less cycles (four or more cycles, 41% vs. 60%; p < 0.01) as well as less second-line chemotherapy (46% vs. 60%; p = 0.02) compared with patients without inflammation. People in the pharmacokinetic cohort with an NLR > 5 had 12¿months less median survival compared with people with an NLR = 5 (6.5 vs. 18¿months; p = 0.08). Similarly, overall survival was significantly shortened in people in the CDCRI cohort receiving carboplatin¿gemcitabine with an NLR > 5 compared with those with an NLR = 5 (7 vs. 12¿months; p < 0.001), and Cox regression analysis showed a 1.5-fold (1.3¿2.1; p < 0.001) increased hazard of death associated with the increased systemic inflammation. Simulations of the newly developed model-based and Calvert dosing assessed the ability to reach this study¿s proposed actual target AUC of 2.2¿2.6¿mg·min/mL. These showed current Calvert dosing was predicted to result in substantial overexposure in patients with high systemic inflammation. The newly developed model showed equivalent levels of carboplatin therapeutic target achievement across the spectrum of inflammation observed in the lung cancer population. Conclusion: An alternate model-based dosing strategy for carboplatin was developed and is predicted to result in consistent drug exposure across the population and improve attainment of therapeutic targets. Further studies of this new model are warranted in people with advanced NSCLC.
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Nova |
2020 |
Liu Z, Galettis P, Broyd SJ, van Hell H, Greenwood LM, de Krey P, et al., 'Model-based analysis on systemic availability of co-administered cannabinoids after controlled vaporised administration', Internal Medicine Journal, 50 846-853 (2020) [C1]
Background: The most important two medicinal cannabinoids are ¿9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic ... [more]
Background: The most important two medicinal cannabinoids are ¿9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic availability, lower individual variability and faster drug delivery. Although it is common THC is co-administered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. Aims: To investigate the influence of different doses of co-administered CBD on the systemic availability of THC, and to compare the availability of THC and CBD in a sample of frequent and infrequent cannabis users. Methods: The study used a randomised, double-blind, crossover placebo-controlled design. THC and/or CBD in ethanol was vaporised and inhaled. Plasma concentrations of THC and CBD were analysed. The THC data created in this study were pooled together with published THC pharmacokinetic data in order to cover all the phases of THC disposition. Population pharmacokinetic model of THC was developed based on the pooled data. The model of CBD was developed based on the data created in this study. Results: Population pharmacokinetic models of THC and CBD were developed. With concomitant inhalation of high-dose CBD, the systemic availability of THC decreased significantly. Frequent cannabis users appeared to have higher systemic availability of THC and CBD when high-dose CBD was administered. Conclusions: The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the ¿real-world¿ setting.
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Nova |
2019 |
O Hara K, Schneider JJ, Jones AL, Wright IMR, Martin JH, Galettis P, 'Development of an UHPLC-MS/MS method for remifentanil quantification in a small plasma volume', Journal of Liquid Chromatography and Related Technologies, 42 521-527 (2019) [C1]
Remifentanil is a short acting opioid currently used in anesthesia and as an analgesic. This paper describes a simple, fast HPLC-MS/MS methodology that allows detection of remifen... [more]
Remifentanil is a short acting opioid currently used in anesthesia and as an analgesic. This paper describes a simple, fast HPLC-MS/MS methodology that allows detection of remifentanil in low volume plasma samples. Acetonitrile protein precipitation is used for sample extraction and clean up. The assay has a lower limit of detection of 0.25 ng/mL and a 3 min run time.
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Nova |
2019 |
Williams M, Martin J, Galettis P, 'A validated method for the detection of synthetic cannabinoids in oral fluid', Journal of Analytical Toxicology, 43 10-17 (2019) [C1]
Workplace drug testing in Australia is governed by two standards AS/NZS 4308:2008 for testing in urine and AS 4760:2006 for oral fluid. These standards are prescriptive and descri... [more]
Workplace drug testing in Australia is governed by two standards AS/NZS 4308:2008 for testing in urine and AS 4760:2006 for oral fluid. These standards are prescriptive and describe the drugs tested, procedures for analysis and collection devices. However, the drugs listed are not exhaustive and workers may consume novel psychoactive substances without detection. Here we present a validated method for the detection and quantitation of 19 synthetic cannabinoids in oral fluid. These drugs are AM2233, JWH-200, AB-005, AB-FUBINACA, AB-PINACA, AB-CHMINACA, AM2201, RCS-4, JWH-250, STS-135, JWH-73, XLR-11, JWH-251, JWH-18, JWH-122, JWH-19, UR-144, JWH-20 and AKB-48. The sample volume is 100 µL and is subject to a rapid, simple, protein precipitation step prior to centrifugation and injection into the LC-MS/MS system. Chromatographic separation was achieved in 4 min on a Kinetex Biphenyl column (50 mm × 3 mm × 2.6 µm) using 0.1% formic acid in water and acetonitrile as the mobile phase. The method was validated with a limit of detection (1 ng/mL) limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (90.5-112.5% of the target concentration) and precision (3-14.7%). This method provides for the rapid detection of synthetic cannabinoids in oral fluid which is readily applicable to a routine laboratory.
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Nova |
2019 |
Solowij N, Broyd S, Greenwood LM, van Hell H, Martelozzo D, Rueb K, et al., 'A randomised controlled trial of vaporised
Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, ¿ 9 -tetrahydrocannabin... [more]
Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, ¿ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400¿mg); THC alone (8¿mg) vs THC combined with low (4¿mg) or high (400¿mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p <.0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users. Trial registration: ISRCTN Registry Identifier: ISRCTN24109245.
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Nova |
2018 |
Solowij N, Galettis P, Broyd SJ, de Krey P, Martin JH, 'Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to Patients in a Hospital Setting', Drugs in R and D, 18 41-44 (2018) [C1]
Background: In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and s... [more]
Background: In many health settings, administration of medicinal cannabis poses significant implementation barriers including drug storage and safety for administering staff and surrounding patients. Different modes of administration also provide different yet potentially significant issues. One route that has become of clinical interest owing to the rapid onset of action and patient control of the inhaled amount (via breath timing and depth) is that of vaporisation of cannabinoid products. Although requiring a registered therapeutic device for administration, this is a relatively safe method of intrapulmonary administration that may be particularly useful for patients with difficulty swallowing, and for those in whom higher concentrations of cannabinoids are needed quickly. A particular concern expressed to researchers undertaking clinical trials in the hospital is that other patients, nurses, and clinical or research staff may be exposed to second-hand vapours in the course of administering vaporised products to patients. Objective: The objective of this study was to take samples from two research staff involved in administering vaporised ¿9-tetrahydrocannabinol to participants in a clinical trial, to examine and quantitate cannabinoid presence. Methods: Blood samples from two research staff were taken during the exposure period for three participants (cannabis users) over the course of approximately 2.5¿h and analysed using tandem mass spectrometry. Results: Blood samples taken over a vaporised period revealed exposure below the limit of detection for ¿9-tetrahydrocannabinol and two metabolites, using tandem mass spectrometry analytical methods. Conclusions: These results are reassuring for hospital and clinical trial practices with staff administering vaporised cannabinoid products, and helpful to ethics committees wishing to quantify risk.
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Nova |
2018 |
Lucas CJ, Galettis P, Song S, Solowij N, Reuter SE, Schneider J, Martin JH, 'Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer', Clinical Therapeutics, 40 (2018)
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2018 |
Martin JH, Schneider J, Lucas CJ, Galettis P, 'Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction?', Clinical Pharmacokinetics, 57 539-545 (2018) [C1]
Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics r... [more]
Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation. Significant recent interest has thus been shown in understanding these pathways to guide the development of agents that inhibit the natural catabolism of endogenous cannabinoids to modify pain and appetite, and to synthesise antagonists for the treatment of disease such as obesity. This research is concurrent with the renewed clinical interest in exogenous cannabinoids and their use in disease. However, the complex pharmacology and physiological effects of exogenous cannabinoids, either as individual components or in combination, as extracts or via administration of the whole plant in humans, are less well known. Yet as with all other therapeutics, including those derived from plants, knowledge of the pharmacokinetics and dynamics of the complete plant, the individual chemical molecules and their synthetic versions, including formulations and excipients is a standard part of drug development. This article covers the key pharmacological knowledge required to guide further exploration of the toxicity and efficacy of different cannabinoids and their formulations in blinded placebo-controlled studies.
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Nova |
2018 |
Solowij N, Broyd SJ, Beale C, Prick J-A, Greenwood L-M, van Hell H, et al., 'Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.', Cannabis Cannabinoid Res, 3 21-34 (2018) [C1]
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Nova |
2018 |
Martin JH, Schneider J, Lucas CJ, Galettis P, 'Exogenous Cannabinoid Efficacy: Merely a Pharmacokinetic Interaction? (vol 57, pg 539, 2018)', CLINICAL PHARMACOKINETICS, 57 645-645 (2018)
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2018 |
Beale C, Broyd SJ, Chye Y, Suo C, Schira M, Galettis P, et al., 'Prolonged Cannabidiol Treatment Effects on Hippocampal Subfield Volumes in Current Cannabis Users.', Cannabis and cannabinoid research, 3 94-107 (2018) [C1]
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Nova |
2018 |
Dryburgh LM, Bolan NS, Grof CPL, Galettis P, Schneider J, Lucas CJ, Martin JH, 'Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects.', British journal of clinical pharmacology, 84 2468-2476 (2018) [C1]
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Nova |
2018 |
Lucas CJ, Galettis P, Schneider J, 'The pharmacokinetics and the pharmacodynamics of cannabinoids.', British journal of clinical pharmacology, 84 2477-2482 (2018) [C1]
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Nova |
2017 |
Williams M, Martin J, Galettis P, 'A validated method for the detection of 32 bath salts in oral fluid', Journal of Analytical Toxicology, 41 659-669 (2017) [C1]
Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tes... [more]
Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tested, devices used and testing methodology followed by the testing agency. However, they are not comprehensive and for many years workers have been able to consume novel psychoactive substances to avoid detection and without consequences. Here, we present a validated method for the detection of 32 Synthetic Stimulant and Hallucogenic drugs, commonly sold as bath salts, in oral fluid. These drugs are cathinone, ephedrone, methylone, flephedrone, MDA, PMA, methedrone, TMA, MDMA, butylone, mephedrone, MDEA, MEC, pentedrone, MBDB, MTA, Alpha-PVP, MPBP, 2C-B, MDPV, DOB, 2C-T-2, TFMPP, DOET, 2C-T-7, naphyrone, MDAI, FMA, DMA, 25C-NBOMe, 25B-NBOMe and 25T4-NBOMe. Sample preparation was undertaken using a simple protein precipitation in acetonitrile. Chromatographic separation was achieved in 7.5 min on a Kinetex F5 column (50mm × 3mm × 2.6 µm) using 0.1% formic acid in water and acetonitrile as the mobile phases. The method was validated with limit of detection (1 ng/mL), limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (85.3-108.4% of the target concentration) and precision (1.9-14%). This method was applied to 12 samples previously submitted for routine testing and two were found to contain 2-CB and DOB (5 and 4 ng/mL) and, MPBP and TFMPP (both at 4 ng/mL). This method provides for the rapid detection of a large number of compounds in oral fluid which is readily applicable to routine testing laboratories.
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Nova |
2016 |
Galettis P, Schneider J, Martin J, 'Care with overseas purchased drugs: devil is in the detail', INTERNAL MEDICINE JOURNAL, 46 1005-1006 (2016)
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2016 |
Schneider J, Galettis P, Williams M, Lucas C, Martin JH, 'Pill testing at music festivals: can we do more harm?', INTERNAL MEDICINE JOURNAL, 46 1249-1251 (2016)
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2016 |
Goulooze SC, Galettis P, Boddy AV, Martin JH, 'Monte Carlo simulations of the clinical benefits from therapeutic drug monitoring of sunitinib in patients with gastrointestinal stromal tumours', CANCER CHEMOTHERAPY AND PHARMACOLOGY, 78 209-216 (2016) [C1]
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Nova |
2013 |
Ehteda A, Galettis P, Pillai K, Morris DL, 'Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice', BMC CANCER, 13 (2013)
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2012 |
Ehteda A, Galettis P, Chu SWL, Pillaii K, Morris DL, 'Complexation of Albendazole with Hydroxypropyl-beta-Cyclodextrin Significantly Improves its Pharmacokinetic Profile, Cell Cytotoxicity and Antitumor Efficacy in Nude Mice', ANTICANCER RESEARCH, 32 3659-3666 (2012)
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2011 |
Luk PP, Galettis P, Links M, 'ERK phosphorylation predicts synergism between gemcitabine and the epidermal growth factor receptor inhibitor AG1478', Lung Cancer, 73 274-282 (2011) [C1]
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2011 |
Manners S, Galettis P, Souza PD, 'Conditions causing gemcitabine crystallization', Journal of Oncology Pharmacy Practice, 17 395-399 (2011)
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2011 |
Mitchell PL, Broad A, Rosenthal MA, Galettis P, Abraham R, Burns I, et al., 'Randomized phase 2 sequencing and pharmacokinetic study of gemcitabine and oxaliplatin in advanced non-small cell lung cancer', Asia-Pacific Journal of Clinical Oncology, 7 376-384 (2011)
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2011 |
Metharom E, Galettis P, Manners S, Jelinek M, Liauw W, De Souza PL, et al., 'The pharmacological advantage of prolonged dose rate gemcitabine is restricted to patients with variant alleles of cytidine deaminase c.79A>C', Asia-Pacific Journal of Clinical Oncology, 7 65-74 (2011)
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2010 |
Pourgholami MH, Cai ZY, Chu SWL, Galettis P, Morris DL, 'The Influence of Ovarian Cancer Induced Peritoneal Carcinomatosis on the Pharmacokinetics of Albendazole in Nude Mice', ANTICANCER RESEARCH, 30 423-428 (2010)
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2010 |
Metharom E, Galettis P, Manners S, Links M, 'Modulation of Gemcitabine Accumulation by DNA-Damaging Agents: Mechanisms and Specificity in an In Vitro Model', ANTICANCER RESEARCH, 30 3669-3673 (2010)
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2010 |
Scott KF, Sajinovic M, Hein J, Nixdorf S, Galettis P, Liauw W, et al., 'Emerging roles for phospholipase A(2) enzymes in cancer', BIOCHIMIE, 92 601-610 (2010)
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2010 |
Pourgholami MH, Szwajcer M, Chin M, Liauw W, Seef J, Galettis P, et al., 'Phase I clinical trial to determine maximum tolerated dose of oral albendazole in patients with advanced cancer', CANCER CHEMOTHERAPY AND PHARMACOLOGY, 65 597-605 (2010)
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2009 |
McPherson RAC, Galettis PT, de Souza PL, 'Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells', BRITISH JOURNAL OF CANCER, 100 649-655 (2009)
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2008 |
Liu JJ, Galettis P, Farr A, Maharaj L, Samarasinha H, McGechan AC, et al., 'In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake', JOURNAL OF INORGANIC BIOCHEMISTRY, 102 303-310 (2008)
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2008 |
Jiang X, Galettis P, Links M, Mitchell PL, McLachlan AJ, 'Population pharmacokinetics of gemcitabine and its metabolite in patients with cancer: effect of oxaliplatin and infusion rate', BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 65 326-333 (2008)
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2007 |
Cai Z-Y, Galettis P, Lu Y, Morris DL, Pourgholami MH, 'Pharmacokinetics of albendazole in New Zealand white rabbits: Oral versus intraperitoneal administration', ANTICANCER RESEARCH, 27 417-422 (2007)
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2007 |
Grimison P, Galettis P, Manners S, Jelinek M, Metharom E, de Souza PL, et al., 'Randomized crossover study evaluating the effect of gemcitabine infusion dose rate: Evidence of auto-induction of gemcitabine accumulation', JOURNAL OF CLINICAL ONCOLOGY, 25 5704-5709 (2007)
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2006 |
Gan HK, Mitchell PL, Galettis P, Davis ID, Cebon J, de Souza P, Links M, 'A phase 1 and pharmacokinetic study of gemcitabine and oxaliplatin in patients with solid tumors', CANCER CHEMOTHERAPY AND PHARMACOLOGY, 58 157-164 (2006)
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2000 |
Screnci D, McKeage MJ, Galettis P, Hambley TW, Palmer BD, Baguley BC, 'Relationships between hydrophobicity, reactivity, accumulation and peripheral nerve toxicity of a series of platinum drugs', BRITISH JOURNAL OF CANCER, 82 966-972 (2000)
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2000 |
McKeage MJ, Berners-Price SJ, Galettis P, Bowen RJ, Brouwer W, Ding L, et al., 'Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes', CANCER CHEMOTHERAPY AND PHARMACOLOGY, 46 343-350 (2000)
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1999 |
Berners-Price SJ, Bowen RJ, Galettis P, Healy PC, McKeage MJ, 'Structural and solution chemistry of gold(I) and silver(I) complexes of bidentate pyridyl phosphines: selective antitumour agents', COORDINATION CHEMISTRY REVIEWS, 185-6 823-836 (1999)
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1999 |
Galettis P, Carr JL, Paxton JW, McKeage MJ, 'Quantitative determination of platinum complexes in human plasma generated from the oral antitumour drug JM216 using directly coupled high-performance liquid chromatography-inductively coupled plasma mass spectrometry without desolvation', JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, 14 953-956 (1999)
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1999 |
Links M, Watson S, Lethlean K, Aherne W, Kirsten F, Clarke S, et al., 'Vinblastine pharmacokinetics in patients with non-small cell lung cancer given cisplatin', CANCER INVESTIGATION, 17 479-485 (1999)
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1999 |
McKeage MJ, Haddad GG, Ding L, Galettis P, Screnci D, Zhuang L, Baguley BC, 'Neuroprotective interactions in rats between paclitaxel and cisplatin', ONCOLOGY RESEARCH, 11 287-293 (1999)
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1998 |
Screnci D, Galettis P, Baguley BC, McKeage MJ, 'Optimization of an ICP-MS assay for the detection of trace levels of platinum in peripheral nerves', ATOMIC SPECTROSCOPY, 19 172-175 (1998)
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1997 |
Screnci D, Er HM, Hambley TW, Galettis P, Brouwer W, McKeage MJ, 'Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin', BRITISH JOURNAL OF CANCER, 76 502-510 (1997)
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1994 |
GALETTIS P, BOUTAGY J, MA DDF, 'DAUNORUBICIN PHARMACOKINETICS AND THE CORRELATION WITH P-GLYCOPROTEIN AND RESPONSE IN PATIENTS WITH ACUTE-LEUKEMIA', BRITISH JOURNAL OF CANCER, 70 324-329 (1994)
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1990 |
GALETTIS P, NORTON RS, 'BIOCHEMICAL AND PHARMACOLOGICAL STUDIES OF THE MECHANISM OF ACTION OF TENEBROSIN-C, A CARDIAC STIMULATORY AND HEMOLYTIC PROTEIN FROM THE SEA-ANEMONE, ACTINIA-TENEBROSA', TOXICON, 28 695-706 (1990)
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