Abstract

The clinical response to drugs may be affected by the simultaneous administration of other drugs that modify the pharmacokinetics and the disposition profile of medications. Drug metabolism via the cytochrome P450 (CYP) system has emerged as an important determinant in the occurrence of several drug-drug interactions. In our earlier studies, Cryptolepis sanguinolenta was reported to cause sub therapeutic blood levels of dihydroartemisinin of artesunate which could lead to decreased effectiveness, and possibly resistance as a result of herb-drug interactions. However, the role of metabolism in such herb-drug interaction has not been studied. Aim: The present study was therefore aimed at determining the effect of Cryptolepis sanguinolenta administration on the metabolism of artesunate. Methods: Reconstituted freeze dried Cryptolepis sanguinolenta was administered in drinking water at the therapeutic dose of 36 mg/kg body weight for two weeks, followed by a single oral dose of artesunate (150 mg/kg body weight). All the animals were sacrificed by cervical dislocation after 24 hr. Liver was excised and microsomes prepared and activities of PNPH, AmD and NOD were determined as a measure of CYP2E1, CYP2B1 and CYP1A activities respectively. Results: Concurrent administration of C. sanguinolenta and artesunate significantly enhanced the activity of CYP1A.