Rifampin

Xiang Y, et al. investigated the drug interaction between the OATP inhibitor rifampin and fluvastatin, a Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1 compound, in 10 healthy volunteers. Intravenous rifampin (600 mg administered over 30 minutes) dramatically altered fluvastatin pharmacokinetics, increasing mean AUC₀–∞ by 255% and peak plasma concentration by 254%, while decreasing the oral volume of distribution by 71%. Notably, elimination half-life, mean absorption time, and time to peak concentration remained unchanged. These findings demonstrate a significant drug interaction despite fluvastatin's BDDCS Class 1 classification, suggesting that the mechanism involves inhibition of hepatic OATP transporters rather than metabolic pathways.

Fig. 1 Average ± SEM plasma concentrations of fluvastatin in 10 healthy volunteers after a single oral dose of 20mg fluvastatin alone, or 20mg oral fluvastatin immediately following a 30-min intravenous infusion of rifampin 600mg. (Xiang Y, et al., 2021)

Smith PB, et al. characterized intravenous rifampin pharmacokinetics in 27 infants with a median gestational age of 26 weeks and postnatal age of 10 days. A one-compartment model best described rifampin disposition, with clearance increasing with body weight and postnatal age. No drug-related adverse events were observed. Simulations based on the final model demonstrated that weight- and age-based dosing regimens (8 mg/kg for infants <14 days postnatal age; 15 mg/kg for those ≥14 days) achieved exposures comparable to therapeutic adult doses for staphylococcal infections and tuberculosis.

Fig. 2 Comparing random effects on clearance (ETA_CL) versus postnatal age of the base (A) and final models (B). (Smith PB, et al, 2019)