Atazanavir/Ritonavir versus Atovaquone
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Study Design
In this study, the pharmacokinetic (PK) interaction between ritonavir boosted atazanavir (ATV/r) and atovaquone was evaluated in HIV-positive adults (n=10). Subjects were randomly assigned to atovaquone 750mg BID with food for 14 days (Phase 1), followed by a washout period and then atovaquone 1500mg BID for 14 days (Phase 2), or vice versa. Blood samples were collected on day 14 of each phase for PK analysis.
A previous open-label, multi center, phase 1 study compared single-dose atovaquone/proguanil 250/100 mg PK between healthy volunteers and HIV-infected volunteers who were stable on ART regimens containing ATV/r (n=19).
Study Results
Using geometric mean ratios and 90% confidence intervals, the AUC and Cavg were both 0.90 (0.67-1.21) when co-administered with ATV/r, compared to atovaquone alone when dosed at 750mg BID. When dosed at 1500mg BID the AUC and Cavg were both 0.95 (0.65-1.38), compared to atovaquone alone.
In the previous study, atovaquone plasma concentrations were modestly lower in those treated with ATV/r. The geometric mean ratio (95% confidence interval) AUC and Cmax for atovaquone relative to healthy volunteers was 0.54 (0.35-0.83) and 0.51 (0.36-0.73), respectively.
PK parameters for ATV/r were not reported.
Study Conclusions
If possible, avoid this combination. If not possible, monitor patient closely for decreased effectiveness of atovaquone.
References
Van Luin M, Van der Ende ME, Richter C, Visser M, Faraj D, Van der Ven A, Kuks PF. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. Aids. 2010; 8: 1223-1226.
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