Docetaxel pharmacokinetics and its correlation with two in vivo probes for cytochrome P450 enzymes: The C 14-erythromycin breath test and the antipyrine clearance test

Abstract

Background: Docetaxel has marked inter-patient PK variability, and metabolic phenotypic probes may enable individualised dosing. This is the first report directly comparing the erythromycin breath test (EBT) (a CYP3A4 probe) with the antipyrine clearance test (ACT), (a general CYP-P450/predominant CYP3A4 probe) for the correlation with docetaxel PK and toxicity. Methods: Patients pretherapy underwent: (A) EBT: IV C 14[N-methyl]-erythromycin was administered and breath samples analysed for 14CO 2, derived parameters included (1) 14CO 2 flux at 10-min (CO 2f 10), (2) 20-min (CO 2f 20), (3) terminal rate constant k CO2 and (4) AUC CO2,(0-∞) and AUC CO2,(0-60). (B) ACL test: patients were given ..