Evaluation of CYP3A activity as a predictive covariate for docetaxel clearance

Baker, Sharyn D.; Tije, Albert J. ten; Carducci, Michael A.; Gelderblom, Hans; Dawkins, F. W.; McGuire, William P.; Verweij, J.

doi:10.1200/jco.2004.22.14_suppl.2006

Cited by 5 publications

(5 citation statements)

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“…Two reports, however, indicate decreased transcriptional activity of CYP3A4*1B [111,112]. No association was observed between the CYP3A4*1B variant and CYP3A activity in studies with healthy subjects using the CYP3A-phenotyping probes midazolam [113][114][115], erythromycin [114,116] and nifedipine [117]. Three other CYP3A4 polymorphisms (CYP3A4*6, CYP3A4*17, and CYP3A4*18) have been shown to result in functional changes in CYP3A activity in vitro [118,119].…”

Section: Cyp3a4/cyp3a5mentioning

confidence: 96%

“…The coadministration of therapeutic drugs which can modulate the CYP3A4 activity can alter the metabolism of anticancer drugs. It has been recently reported that liver function together with the concentration of the acute-phase reactant, α-1 acid glycoprotein, explained up to 18% of overall variation in CYP3A activity [116].…”

Section: Phenotypic Variation Of Cyp3a4 Activity Related To Pharmacokmentioning

confidence: 99%

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Cytochrome P450 and Anticancer Drugs

Fujita

2006

CDM

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Cytochrome P450 (CYP) is involved in the metabolism of a variety of anticancer drugs. CYP activities are known to be modified by several factors including genetic polymorphisms, changes in physiological conditions such as age, disease status or intake of certain drugs or foods or environmental factors such as smoking. These factors may cause interindividual differences in the pharmacokinetic profiles of anticancer drugs, leading to the variations of efficacy or toxicity of the drugs. Genetic polymorphisms present in CYPs sometimes result in the reduced activity of the enzymes causing low metabolic clearance of drugs or low production of active metabolites. For example, the formation of endoxifen, which is an active metabolite of tamoxifen, was less in patients with inactive polymorphic CYP2D6 than those with the wild type enzyme. CYP3A is the most abundant CYP expressed in the human liver and the small intestine that is involved in the metabolism of various anticancer drugs. The catalytic activity of CYP3A shows a large interindividual variability giving rise to large interindividual differences in the pharmacokinetic profiles of some anticancer drugs. So far, many attempts have been made to monitor the phenotypic activity of CYP3A in order to reduce the pharmacokinetic variations of anticancer drugs. Erythromycin, midazolam and cortisol are commonly used to monitor in vivo hepatic CYP3A activity. These methods have been applied to reduce the pharmacokinetic variations of docetaxel. Drug-drug interactions related to CYPs also modulate the pharmacokinetic profiles of anticancer drugs. These factors should be considered when trying to optimize and individualize chemotherapy.

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Section: Cyp3a4/cyp3a5mentioning

confidence: 96%

Section: Phenotypic Variation Of Cyp3a4 Activity Related To Pharmacokmentioning

confidence: 99%

Cytochrome P450 and Anticancer Drugs

Fujita

2006

CDM

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“…Wide intersubject variation in liver CYP3A4 activity has been observed in cancer patients (50-fold) which has been attributed to many factors including disease stage, multiple co-medications leading to drug interactions, and environmental factors [6]. To comprehensively characterize CYP3A4-mediated metabolism of sorafenib in cancer patients and the contribution of the principal metabolite sorafenib N-oxide to drug toxicity and efficacy, the quantitation of both analytes in human plasma was necessary.…”

Section: Introductionmentioning

confidence: 99%

Quantitation of sorafenib and its active metabolite sorafenib N-oxide in human plasma by liquid chromatography–tandem mass spectrometry

Zhao

Navid

et al. 2010

Journal of Chromatography B

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A simple and rapid method with high performance liquid chromatography/tandem mass spectrometry is described for the quantitation of the kinase inhibitor sorafenib and its active metabolite sorafenib N-oxide in human plasma. A protein precipitation extraction procedure was applied to 50 µL of plasma. Chromatographic separation of the two analytes, and the internal standard [ 2 H 3 13 C]-sorafenib, was achieved on a C 18 analytical column and isocratic flow at 0.3 mL/min for 4 min. Mean within-run and between-run precision for all analytes were <6.9 % and accuracy was <5.3%. Calibration curves were linear over the concentration range of 50 to 10,000 ng/mL for sorafenib and 10 to 2,500 ng/mL for sorafenib N-oxide. This method allows a specific, sensitive, and reliable determination of the kinase inhibitor sorafenib and its active metabolite sorafenib N-oxide in human plasma in a single analytical run.

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“…(Table 3) In this study we failed to identify a correlation between Docetaxel PK and the EBT parameters, regardless of regimen. The EBT has been inconsistently correlated with Docetaxel clearance (CL Doc ), [1,3,[20][21]38] and similarly did not correlate with CL Doc in another study with the weekly regimen. [35] A population model has also evaluated the relationship between CYP3A4 activity (using the EBT) and CL Doc in 77 patients with varying degrees of liver function.…”

Section: Discussionmentioning

confidence: 99%