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  • Title: Pharmacokinetics and inhibitory quotient of atazanavir/ritonavir versus lopinavir/ritonavir in HIV-infected, treatment-naive patients who participated in the CASTLE Study.
    Author: Zhu L, Liao S, Child M, Zhang J, Persson A, Sevinsky H, Eley T, Xu X, Krystal M, Farajallah A, McGrath D, Molina JM, Bertz R.
    Journal: J Antimicrob Chemother; 2012 Feb; 67(2):465-8. PubMed ID: 22121190.
    Abstract:
    OBJECTIVES: To characterize the pharmacokinetics and inhibitory quotient (IQ) of atazanavir/ritonavir- and lopinavir/ritonavir-based regimens in HIV-infected, treatment-naive patients. METHODS: The CASTLE Study was a 96 week randomized study comparing 300 mg of atazanavir once daily with 400 mg of lopinavir twice daily, each with low-dose ritonavir (100 mg) plus tenofovir disoproxil fumarate/emtricitabine in HIV-infected, treatment-naive patients. A subset of patients participated in an intensive pharmacokinetic evaluation of the atazanavir regimen (n = 18) and the lopinavir regimen (n = 21) at week 4. (ClinicalTrials.gov NCT00272779) RESULTS: Atazanavir geometric mean (CV%) C(max), C(min) and AUC over the dosing interval were 2897 (46) ng/mL, 526 (57) ng/mL and 28 605 (46) ng · h/mL, respectively, and for lopinavir they were 10 655 (51) ng/mL, 5944 (68) ng/mL and 90 946 (59) ng · h/mL, respectively. The baseline protein binding-adjusted 90% effective concentration (PBA-EC(90)) was 16 (44) ng/mL for atazanavir and 173 (44) ng/mL for lopinavir. The median IQ (min, max), calculated as the ratio of C(min) to individual baseline PBA-EC(90), was 35 (4, 77) for atazanavir and 34 (11, 129) for lopinavir. The C(max) for ritonavir was 46% higher, while AUC(0-24) and C(min) were 16% and 72% lower in the atazanavir regimen compared with the lopinavir regimen. Tenofovir exposures were similar with both treatments. CONCLUSIONS: Atazanavir (300 mg once daily) and lopinavir (400 mg twice daily), each with low-dose ritonavir, achieved similar IQs in HIV-infected, treatment-naive patients. These results are supportive of the main clinical finding of the CASTLE Study, that the atazanavir/ritonavir-based regimen is non-inferior in antiviral efficacy to the lopinavir/ritonavir-based regimen in antiretroviral-naive subjects.
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