The objective of this study was to investigate the effect of Sutherlandia frutescens (SF) on the bioavailability of atazanavir (ATV) in twelve healthy male subjects. During Phase I (Day 1), subjects ingested a single dose of ATV and blood samples were drawn before dose and at 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 9.0, 12, 18, and 24 hours after dose. From Day 3 to Day 14, a single dose of milled SF was administered twice daily to each subject. During Phase II, Day 15, subjects ingested single doses of ATV and SF. Blood samples were drawn as previously described. Plasma was harvested from blood samples and the concentration of ATV therein was determined. For each phase, the mean ATV plasma concentration-time profile was plotted and the means of and for ATV were computed. The geometric mean ratios and confidence intervals (CIs) for and were 0.783 (0.609–1.00) and 0.801 (0.634–1.01), respectively. The CIs for both PK parameters fell below the limits of the “no-effect” boundary, set at 0.8–1.25, indicating that SF significantly reduced the bioavailability of ATV. This may potentially result in subtherapeutic plasma concentrations and thus reduced anti-HIV efficacy of ATV. 1. Introduction The use of African traditional medicines (ATMs) by HIV/AIDS patients in South Africa is a common phenomenon [1–4]. Anecdotal reports detail the use of the indigenous South African plants, Hypoxis hemerocallidea (African potato) and Sutherlandia frutescens (SF) for the treatment of HIV/AIDS . Despite the widespread use of ATMs, the impact of these medicines on the safety and efficacy of antiretrovirals (ARVs) when used concurrently has not yet been fully determined. The protease inhibitor (PI), atazanavir (ATV), has a favourable adverse effect profile in comparison to lopinavir; therefore it has been included in the South African clinical guidelines for the management of HIV/AIDS in adults and adolescents (2010), as an alternative to lopinavir in patients who experience intolerable gastrointestinal problems, hyperlipidaemia or hyperglycemia . Like other PIs, ATV is a substrate of the efflux transporter, P-gp [7, 8], which has a role to play in mediating absorption in the small intestine, as well as CYP3A4 and CYP3A5  which facilitate metabolism in the small intestine and liver. ATV may thus be susceptible to pharmacokinetic (PK) interactions with agents able to modulate the activities of this transporter and family of CYP enzymes. SF is a South African plant which has a long history of use in the practice of traditional medicine, particularly by the
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