The Use of Microdosing for In vivo Phenotyping of Cytochrome P450 Enzymes: Where Do We Stand? A Narrative Review
European journal of drug metabolism and pharmacokinetics April 30, 2024 L. T. van der Heijden, F. Opdam, J. H. Beijnen et al.
Cytochrome P450 (CYP) enzymes are responsible for breaking down about 80% of medications, and differences in their activity between people can affect drug exposure and treatment outcomes. Measuring CYP activity in the body (phenotyping) typically uses therapeutic or subtherapeutic drug doses that can cause side effects. This review examined whether using microdoses (100 µg) of drug substrates could safely assess CYP activity. Based on current evidence, microdosing is not recommended for phenotyping CYP1A2, CYP2C9, CYP2D6, or CYP2E1. However, it can be used for CYP2C19 and CYP3A. For CYP2C19, a single 100 µg dose of omeprazole with a 24-hour blood level measurement is suggested. For CYP3A, a 0.1–75 µg dose of midazolam, measuring its clearance or area under the curve, is recommended.