Inhibition of cytochrome P450 3A enzyme by Millettia aboensis: its effect on the pharmacokinetic properties of efavirenz and nevirapine

ABSTRACT The chronic and comorbid nature of HIV infection necessitate the use of multiple drugs including herbs to relieve symptoms with a possible increase in herb–drug interaction cases. This study was designed to evaluate the effect of Millettia aboensis (Hook. f.) Baker, Fabaceae, on cytochrome P450 3A isoenzyme and the influence of this effect on the bioavailability of two antiretroviral agents. In vitro effect of ethanol extract of M. aboensis on intestinal and liver microsomes extracted from female rats was assessed using erythromycin-N-demethylation assay method while in vivo effects were determined by estimating simvastatin plasma concentrations in rats. The effect of the extract on pharmacokinetic parameters of orally administered efavirenz (25 mg/kg) and nevirapine (20 mg/kg) was determined in rats divided into groups (n = 5). Plasma drug concentrations were assayed using HPLC and pharmacokinetic parameters determined through a non-compartmental analysis as implemented in WinNonlin pharmacokinetic program. The extract inhibited both intestinal and liver microsomal cytochrome P450 3A isoenzyme activities in vitro and enhanced simvastatin absorption in vivo with possible inhibition of metabolizing enzymes as indicated by significant (p < 0.05) increase in maximal concentration, area under curve and mean resident time of the drug. However, further in vivo interaction studies in animal model did not produce significant (p > 0.05) changes in the pharmacokinetic parameters of efavirenz and nevirapine. HPLC fingerprinting indicated the presence of quercetin and kaempferol in the extract. These findings revealed M. aboensis as an inhibitor of cytochrome P450 3A enzyme but, with no significant effect on the bioavailability of orally administered nevirapine and efavirenz.

A comparative study of quinine and artemether in the treatment of severe malaria in Nigerian children

Purpose: Nigeria has adopted quinine as the drug of first choice in the treatment of severe malaria and artemether as an alternative therapy. The purpose of this study was to ascertain whether artemether is a comparable alternative to quinine in the management of severe malaria in Nigerian children. Methods: We conducted a randomized prospective study comparing quinine and artemether therapies in 90 Nigerian children with severe malaria. Results: Mortality was lower in quinine group (13.0) than artemether (15.9); Odds Ratio (OR) = 0.446 (95Confidence Interval (CI); 0.124 to 1.603; p = 0.249 ). The parasitaemia clearance on day 3 by quinine and artemether was 96.8 and 99.0(p = 0.422); respectively; while on day 14 it was 100for both medicines. Fever clearance by quinine and artemether was 87.7 and 90(p = 0.753); respectively; on day 3 but it increased to 100 and 96.42(p = 0.072); respectively; on day 14. For the quinine group; 71.74of the patients spent less than one week in the hospital versus 61.76for the artemether group (p = 0.829; OR = 0.883; 95CI = 0.284 to 2.742). Conclusion: Artemether is a comparable alternative to quinine in the treatment of severe paediatric malaria