Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers

Abstract

Purpose

To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans.

Methods

Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography–tandem mass spectrometry methods.

Results

Coadministration of nemonoxacin with probenecid reduced the renal clearance (CL _r) of nemonoxacin by 22.6%, and increased the area under the plasma concentration–time curve from time 0 to infinity (AUC _0−∞) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CL _r of nemonoxacin by 13.3% and increased AUC _0−∞ by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine.

Conclusion

Although probenecid reduced the CL _r and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin.