Pharmacokinetics of a novel trioxane antimalarial drug 99/411: alterations upon rifampicin coadministration, single and multiple oral dose drug–drug interactions in Sprague-Dawley rats

Abstract

Aim: Study was aimed to investigate the potential drug–drug interactions between antimalarial candidate 99/411 and antitubercular drug rifampicin. Methods: A single-dose drug-interaction study followed by multiple dose parallel study was designed to estimate the drug–drug interactions. Results: It was found that steady-state pharmacokinetics profile of 99/411 determined after multiple dosing for five successive days was consistent with the single-dose characteristics in both the cases, when 99/411 was given alone and co-administered with rifampicin. Conclusion: The compound was absorbed fast after each dosing and declined up to next 24 h to lower concentration. AUC showed accumulation of 99/411 day by day after multiple dosing, which may affect the therapeutic response of this molecule.