Coadministration of Lopinavir/Ritonavir and Phenytoin Results in Two-Way Drug Interaction Through Cytochrome P-450 Induction

Abstract

Lopinavir/ritonavir (LPV/RTV) is a CYP3A4 inhibitor and substrate; it also may induce cytochrome P-450 (CYP) isozymes. Phenytoin (PHT) is a CYP3A4 inducer and CYP2C9/CYP2C19 substrate. This study quantified the pharmacokinetic (PK) drug interaction between LPV/RTV and PHT. Open-label, randomized, multiple-dose, PK study in healthy volunteers. Subjects in arm A (n = 12) received LPV/RTV 400/100 mg twice daily (BID) (days 1–10), followed by LPV/RTV 400/100 mg BID + PHT 300 mg once daily (QD) (days 11–22). Arm B (n = 12) received PHT 300 mg QD (days 1–11), followed by PHT 300 mg QD + LPV/RTV 400/100 mg BID (days 12–23). Plasma samples were collected on day 11 and day 22; PK parameters were compared by geometric mean ratio (GMR, day 22:day 11). P values 0-12h