Pharmacokinetics of Atazanavir in Ritonavir-boosted Combination in Asian Healthy Volunteers: Comparisons between the Standard and Reduced Doses of Both Agents

Atazanavir/ritonavir (ATV/r) 200/100 mg once-daily (OD) has been shown comparable in drug exposure to the standard dose in Asian study. We explored the pharmacokinetic profiles of the boosting effect of ritonavir at 50 mg to either atazanavir 300 or 200 mg in 32 adult Thai healthy volunteers. The geometric means (GM) of ATV AUC0-24 were 40.66, 25.50 and 24.97 mg-h/L and Cmin were 0.53, 0.27 and 0.24 mg/L for 300/100, 300/50 and 200/50 mg OD doses, respectively. Subjects while taking ATV/r 300/50 and 200/50 mg OD had ATV AUC0-24 and Cmin significantly lower than when 300/100 mg was taken (P < 0.05). The GM of bilirubin concentrations were significantly reduced 2.46 vs 1.48 mg/dL for 300/50 mg and 2.60 vs 1.36 mg/dL for 200/50 mg (P = 0.001). The reduced dose of ATV/r decreased in ATV AUC0-24, Cmin and the rate of hyperbilirubinaemia. However, one-third of subjects taken either ATV/r 300/50 or 200/50 had subtherapeutic ATV levels, boosted with 50 mg RTV is therefore not recommended.