icon_folder.gif   Conference Reports for NATAP  
  ICAAC 41st Interscience Conference on Antimicrobial Agents and Chemotherapy
Chicago, Illinois, December 16-19
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Abstract 489. Amprenavir (APV) Plasma and Intracellular Concentrations When Co-Administered with Ritonavir (RTV) in Twice and Once Daily Regimens in HIV-Infected Patients
Reported by Jules Levin
  This study was reported by R Garraffo and GlaxoSmithKline. APV/RTV twice and once daily dosing is being studied in clinical trials. This study at ICAAC reported the changes in blood levels of APV and RTV when used in combination at once and twice daily dosing. This was a phase 1, open-label, multiple dosing study with 3 regimen periods. 10 HIV-infected patients received the following 3 treatments for a minimum of ten days: APV 1200mg bid (twice daily), APV 600/RTV 100mg bid, APV 1200/RTV 200mg QD (once daily). Subjects continued their ART including NNRTIs. However, other PIs were not permitted during the study. Blood samples for APV and RTV plasma determination were collected at pre-dose, 0.5, 1, 2, 4, 6, 8 and 10 hours. Additional samples were performed at 22 and 24 hour for QD regimen. Blood samples for APV intracellular determinations in PBMCs were collected at pre-dose, 2 and 22 hours (only for QD regimen) after dosing.
Demographic Characteristics of Patients
age: 39
weight: 69 kg
CD4: 419
HIV-RNA: 2.73 log (<1.6-5.90 range)
All patients took NRTIs including NNRTIs: Efavirenz (n=1), NVP (n=1).
APV Steady State PK Parameters
  APV Steady State PK Parameters  
  Authors reported APV exposure was highly increased; particularly, Cmin was 7 times higher (APV/RTV bid regimen) and 4 times higher (APV/RTV qd regimen) than APV 1200mg without modification of APV Cmax and Tmax. APV clearance was decreased by more than 50%. the principal effect of RTV is seen on APV hepatic metabolism rather than APV intestinal absorption. Seven subjects (7/10) receiving APV 1200mg bid alone presented APV intracellular concentrations under the limit of quantification, vs 1 patient in APV/RTV bid regimen and none in APV/RTV qd regimen. Cmin ratios were above 1 in the two regimen using RTV co-administration, and the highest ratio was obtained by APV/RTV qd. PK parameters were not altered by APV. None of the treatment combinations were associated with an increased number of adverse events or clinically significant lab abnormalities.