Effect of short term and chronic administration of Sutherlandia frutescens on pharmacokinetics of nevirapine in rats

摘要

Sutherlandia frutescens (sutherlandia), an African herbal supplement is currently recommended by the South African Ministry of Health for the treatment of AIDS patients. However, no reports yet exist delineating the effect of sutherlandia on pharmacokinetics of antiretroviral agents. Therefore, this investigation aimed at screening the effects of short term and chronic exposure of sutherlandia on oral bioavailability and pharmacokinetics of nevirapine (NVP), a non nucleoside reverse transcriptase inhibitor, in Sprague Dawley rats. NVP (6 mg/kg) was administered orally alone (control) and with co-administration of sutherlandia; short term (12 mg/kg single dose) and long term (12mg/kg, once a day for 5 days). No significant difference in the pharmacokinetic parameters of NVP was found upon short term co-administration of Sutherlandia. However, there was a 50% decrease (p < 0.05) in the AUC and Cmax values of NVP after 5 days of chronic exposure with Sutherlandia. In addition, quantitative RT-PCR studies demonstrated a 2–3 fold increase in the hepatic and intestinal mRNA expression of CYP3A2, relative to vehicle control. To further confirm, if this could translate into a clinically relevant pharmacokinetic interaction in patients, we tested this hypothesis employing LS-180 cells as an in vitro induction model for human CYP3A4. Ninety six hours post treatment, similar to positive control rifampicin (25µM), sutherlandia extract (300µg/mL) resulted in elevated m-RNA expression levels and functional activity of CYP3A4 (human homologue of rodent CYP3A2) in LS-180 cells. Taken together, these results suggest that a potential drug-herb interaction is possible when NVP is co-administered with sutherlandia frutescens, although this hypothesis still remains to be investigated in a clinical setting.