CYP3A and CYP2C19 Activity Determined by Microdosed Probe Drugs Accurately Predict Voriconazole Clearance in Healthy Adults.

ABSTRACT:

Background and objective

Voriconazole is an important broad-spectrum anti-fungal drug with nonlinear pharmacokinetics. The aim of this single centre fixed-sequence open-label drug-drug interaction trial in healthy participants (N = 17) was to determine whether microdosed probe drugs for CYP3A and CYP2C19 reliably predict voriconazole clearance (CL_VRZ).

Methods

At baseline, a single oral microdose of the paradigm substrates midazolam (CYP3A) and omeprazole (CYP2C19) were given to estimate their clearances (CL). Thereafter, a single oral dose of voriconazole was administered (50, 100, 200 or 400 mg), followed by the microdosed probe drugs.

Results

The clearances of midazolam (CL_MDZ 790-2790 mL/min at baseline; 248-1316 mL/min during voriconazole) a

SUBMITTER: Muhareb A 

PROVIDER: S-EPMC10450012 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature