title: Pharmacokinetics and inhibitory quotient of atazanavir/ritonavir versus lopinavir/ritonavir in HIV-infected, treatment-naive patients who participated in the CASTLE Study.
abstract: OBJECTIVE
  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.
authors: Bristol-Myers Squibb, Research and Development, Princeton, NJ, USA. li.zhu@bms.com
authors: Li
authors: L
authors: Zhu
authors: Shanmei
authors: S
authors: Liao
authors: Michael
authors: M
authors: Child
authors: Jenny
authors: J
authors: Zhang
authors: Anna
authors: A
authors: Persson
authors: Heather
authors: H
authors: Sevinsky
authors: Timothy
authors: T
authors: Eley
authors: Xiaohui
authors: X
authors: Xu
authors: Mark
authors: M
authors: Krystal
authors: Awny
authors: A
authors: Farajallah
authors: Donnie
authors: D
authors: McGrath
authors: Jean-Michel
authors: JM
authors: Molina
authors: Richard
authors: R
authors: Bertz
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000069446:Atazanavir Sulfate; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D063065:Organophosphonates / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D003841:Deoxycytidine; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir