Effect of Modulation of Uridine 5’-Diphospho-Glucuronosyl Transferase 1A Enzymes by Jatropha curcas Extracts on the Pharmacokinetics of Dolutegravir

Abstract Purpose Concomitant herbal medicine and antiretroviral therapy can result in adverse effects or diminished drug efficacy. This study determined the effect of Jatropha curcas on UGT1A activity and its implications on dolutegravir (DTG) pharmacokinetics during concomitant administration.Methods The effects of aqueous (AJC) and ethanol (EJC) extracts of J. curcas were evaluated in rat liver microsomes, and UGT1A activity was determined using spectrophotometric techniques. Eighty Wistar rats were divided into five groups: control group (water ad libitum, then DTG, 10 mg/kg on day 7), AJC pretreatment (PT) group (AJC 200 mg/kg for 7 days + DTG 10 mg/kg on day 7), EJC PT group (EJC 200 mg/kg for 7 days + DTG 10 mg/kg on day 7), AJC co-administration group (CA) (AJC 200 mg/kg + DTG 10 mg/kg for 7 days), and EJC CA group (EJC 200 mg/kg + DTG 10 mg/kg). On day 8, blood samples were collected at different time intervals and plasma concentration of DTG was determined using high liquid chromatography.Results AJC and EJC caused moderate in vitro inhibition of UGT1A activity with IC50 88.02 ± 3.41 and 79.09 ± 1.03 respectively. Co-administration of AJC and EJC with dolutegravir demonstrated a significant increase in area under the curve concentration (AUC) and maximum plasma concentration of (Cmax) of dolutegravir.Conclusion It was observed from the result that the co-administration of AJC and EJC with DTG in Wistar rats, triggered herb-drug interactions. Thus, J. curcas extracts should be used with caution by HIV patients on DTG therapy.