Lack of Potential Pharmacokinetic and Pharmacodynamic Interactions Between Piragliatin, a Glucokinase Activator, and Simvastatin in Patients With Type 2 Diabetes Mellitus.

ABSTRACT

To evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD, glucose-lowering effect) interaction between simvastatin and piragliatin, both CYP3A substrates, 30 patients with type 2 diabetes mellitus participated in this open-label, randomized, 6-sequence, 3-way crossover (William's design) study. During 3 periods, patients were randomized to receive a single dose of 80 mg simvastatin alone, a single dose of 100 mg piragliatin alone, as well as single doses of 80 mg simvastatin and 100 mg piragliatin together. Primary PK and PD parameters were AUCs on dosing days. The ratio of geometric means (90% confidence intervals) of the AUCinf of piragliatin coadministered with simvastatin compared with piragliatin alone was 0.98 (0.92-1.05), whereas that of the AUCinf of simvastatin acid (active metabolite) coadministered with piragliatin compared with simvastatin alone, was 1.02 (0.90-1.16), suggesting lack of pharmacokinetic interaction between piragliatin and simvastatin. Piragliatin's glucose-lowering effect was not affected by coadministration of simvastatin. Overall, administration of piragliatin with simvastatin was without additional clinically relevant adverse effects as well as abnormality in laboratory tests, vital signs, and electrocardiogram parameters. Concomitant administration of simvastatin and piragliatin, both CYP3A substrates, has no clinically relevant effect on the pharmacokinetics of either piragliatin or simvastatin or on the pharmacodynamics for piragliatin.