Coadministration of Rifampin Significantly Reduces Odanacatib Concentrations in Healthy Subjects.

This open-label 2-period study assessed the effect of multiple-dose administration of rifampin, a strong cytochrome P450 3A (CYP3A) and P-glycoprotein inducer, on the pharmacokinetics of odanacatib, a cathepsin K inhibitor. In period 1, 12 healthy male subjects (mean age, 30 years) received a single dose of odanacatib 50 mg on day 1, followed by a 28-day washout. In period 2, subjects received rifampin 600 mg/day for 28 days; odanacatib 50 mg was coadministered on day 14.

Pitavastatin is a more sensitive and selective organic anion-transporting polypeptide 1B clinical probe than rosuvastatin.

Aims: Rosuvastatin and pitavastatin have been proposed as probe substrates for the organic anion-transporting polypeptide (OATP) 1B, but clinical data on their relative sensitivity and selectivity to OATP1B inhibitors are lacking. A clinical study was therefore conducted to determine their relative suitability as OATP1B probes using single oral (PO) and intravenous (IV) doses of the OATP1B inhibitor rifampicin, accompanied by a comprehensive in vitro assessment of rifampicin inhibitory potential on statin transporters.

Methods: The clinical study comprised of two separate panels of eight healthy subjects.

Absence of clinically relevant drug-drug interaction between odanacatib and digoxin after concomitant administration.

Objectives: This study was conducted in order to assess the effect of multiple doses of odanacatib, a cathepsin (Cat)-K inhibitor, on the pharmacokinetics of digoxin.

Materials: Twelve healthy male and female subjects received 0.5 mg digoxin and 50 mg odanacatib.