Please use this identifier to cite or link to this item: https://doi.org/10.1200/JCO.2002.01.025
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dc.titleExplaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies
dc.contributor.authorGoh, B.-C.
dc.contributor.authorLee, S.-C.
dc.contributor.authorWang, L.-Z.
dc.contributor.authorFan, L.
dc.contributor.authorGuo, J.-Y.
dc.contributor.authorLamba, J.
dc.contributor.authorSchuetz, E.
dc.contributor.authorLim, R.
dc.contributor.authorLim, H.-L.
dc.contributor.authorOng, A.-B.
dc.contributor.authorLee, H.-S.
dc.date.accessioned2014-10-29T01:52:44Z
dc.date.available2014-10-29T01:52:44Z
dc.date.issued2002-09-01
dc.identifier.citationGoh, B.-C., Lee, S.-C., Wang, L.-Z., Fan, L., Guo, J.-Y., Lamba, J., Schuetz, E., Lim, R., Lim, H.-L., Ong, A.-B., Lee, H.-S. (2002-09-01). Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. Journal of Clinical Oncology 20 (17) : 3683-3690. ScholarBank@NUS Repository. https://doi.org/10.1200/JCO.2002.01.025
dc.identifier.issn0732183X
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/105941
dc.description.abstractPurpose: To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype. Patients and Methods: We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435Tpolymorphism of MDR1. Results: Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5′ regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients. Conclusion: Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further. © 2002 by American Society of Clinical Oncology.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1200/JCO.2002.01.025
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentPHARMACY
dc.description.doi10.1200/JCO.2002.01.025
dc.description.sourcetitleJournal of Clinical Oncology
dc.description.volume20
dc.description.issue17
dc.description.page3683-3690
dc.description.codenJCOND
dc.identifier.isiut000178178100020
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