Pharmacokinetic parameters of atazanavir in ritonavir-boosted combination therapy in Thai healthy volunteers : comparison between reduced doses of ritonavir or atazanavir

Abstract

The standard dose of atazanavir (ATV)/ritonavir (RTV) 300/100 mg once daily results in higher ATV exposure in Thai populations. This study was to compare the pharmacokinetic (PK) parameters and hyperbilirubinemia when lower than standard dose of ATV/RTV was given in 31 adults Thai healthy volunteers. Subjects were randomly assigned into 2 groups who were administered with the different doses of ATV/RTV (group I: 300/100 vs. 300/50, group II: 300/100 vs. 200/50). There were no statistically significant differences between the two groups in demographic data. The geometric means (GM) of ATV for 300/100, 300/50 and 200/50 mg once daily doses, respectively, were as follows: AUC₀₋₂₄(mg-h/L) 40.66, 25.50, 24.97; C[subscript max](mg/L) 4.12, 2.83, 2.58; C[subscript min](mg/L) 0.53, 0.27, 0.24, respectively. ATV AUC₀₋₂₄, C[subscript max] and C[subscript min] for 300/50 and 200/50 mg were statistically significant lower than 300/100 mg but did not show significantly different between 300/50 and 200/50 mg. ATV C[subscript min] for 300/100, 300/50 and 200/50 mg, respectively, were as follow: in subtherapeutic (%) 0, 31, 33; within therapeutic range (%) 74, 56,67; overtherapeutic (%) 26, 13, 0, respectively. There was significantly decrease in bilirubin concentration after dose reduction. Therefore, the reduced dose of ATV/RTV resulted in decreasing in both ATV C[subscript min] and hyperbilirubinemia. However, further investigation in Thai HIV-infected patients is required.