Background: ABT-378/r is an HIV-protease inhibitor with high antiretroviral activity at clinical dose of 400/100 mg BID. ABT-378/r liquid (80/20mg/mL) and soft elastic capsule (SEC, 133/33mg) co-formulations (4:1 ratio) are planned for commercial use.

Methods: A 4-period randomized crossover study in 54 healthy subjects examined bioequivalence and food effects for single 400/100mg doses of ABT-378/r clinical co-formulations. Regimen A: 3 SECs/nonfasting (500 Kcal, 25% fat). Regimen B: 3 SECs/fasting. Regimen C: 5 mL liquid/nonfasting. Regimen D: 5 mL liquid/fasting. For nonfasting regimens, subjects began breakfast 30 min before dosing. For fasting regimens, subjects fasted for 10 h prior and 4 h after dosing. Plasma levels were measured using LC/MS/MS. Pharmacokinetics were assessed with noncompartmental methods. Regimens compared using linear mixed effects model and two one-sided tests via 90% confidence intervals (CI) for log-transformed variables.

Results: For bioequivalence (Regimen C to A), ABT-378 AUC and Cmax point estimates (CI) were 0.894 (0.805-0.992) and 0.920 (0.836-1.012), respectively. For SEC food effect (Regimen B to A), the ABT-378 AUC point estimate (CI) was 0.640 (0.563–0.727); for liquid (Regimen D to C), it was 0.557 (0.490-0.632). Previously, ABT-378 bioavailability at ABT-378/r 400/200 mg SEC dose appeared to be similar fasting and nonfasting. Results suggest ritonavir dose size may influence the degree of ABT-378 food effect.

Conclusions: Under nonfasting conditions, the liquid was bioequivalent to the SECs. For the SEC and liquid, ABT-378 AUCs were 36 and 44% lower, respectively, when administered fasting compared to a moderate fat meal. Administration of both liquid and SEC ABT-378/r co-formulations with food improves ABT-378 bioavailability.

Abbott Laboratories, Abbott Park, IL

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