An inverse Gaussian density function-input model linked to a 2-compartment open distribution model with first-order elimination from the central compartment was appropriate to describe complex absorption and disposition kinetics of enfuvirtide plasma concentration-time data after subcutaneous administration to patients with HIV infection. Enfuvirtide was nearly completely absorbed from subcutaneous depot, and pharmacokinetic parameters were linear up to a dose of 180 mg in this study.

The effect of saquinavir-boosted ritonavir at therapeutic (1000/100 mg twice daily [bid]) and supratherapeutic (1500/100 mg bid) doses was evaluated in a double-blind, placebo- and positive-controlled (moxifloxacin 400 mg) 4-way crossover thorough QT/QTc study. Least squares mean estimated study-specific QTc (QTcS) change from dense predose baseline (ddQTcS(dense)) was the primary endpoint. Greatest mean increase in ddQTcS(dense) occurred 12 hours postdose for the 1000/100-mg group (18.9 ms) and 20 hours for the 1500/10-mg group (30.2 ms). The upper 1-sided 95% confidence interval was >20 ms from 2 to 20 hours postdose in both groups. ddQTcB(dense) and ddQTcF(dense) were similar to ddQTcS(dense). No QTcS, QTcF, or QTcB measurements were >500 ms. One participant receiving 1000/100 mg and 3 receiving 1500/100 mg had a maximum ddQTcS(dense) >60 ms. More participants with ≥1 adverse event received saquinavir/ritonavir. PubMed search and Roche postmarketing data did not reveal publications or reports directly presenting the effect of saquinavir on QT/QTc or causing torsade de pointes.

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The primary objective was to determine whether rifampicin influences the pharmacokinetics of enfuvirtide in HIV-1-infected patients. In a single-center, open-label, one-sequence crossover, clinical pharmacology study, 12 HIV-1-infected adults received enfuvirtide (90 mg, twice daily) on days 1 to 3 and days 11 to 13 (morning dose only on days 3 and 13) and rifampicin (600 mg, once daily) from days 4 to 13. Plasma concentrations were measured for enfuvirtide and its metabolite (days 3 and 13) and rifampicin (day 13 only). The ratios of least squares means (LSM) and 90% confidence intervals for enfuvirtide and enfuvirtide metabolite pharmacokinetic parameters (AUC12h, Cmax, Ctrough) were estimated in the presence and absence of rifampicin. Treatments were compared using an analysis of variance for natural log-transformed variables, with factors patient and treatment. Efficacy and safety were also monitored. Steady-state rifampicin had no appreciable effect on any of the pharmacokinetic parameters assessed for either enfuvirtide or its metabolite. The ratio of LSM for AUC12h, Cmax, and Ctrough for enfuvirtide was 97.5%, 103%, and 84.9%, respectively, and 108%, 112%, and 92.9%, for the enfuvirtide metabolite. Rifampicin did not affect the t1/2 of enfuvirtide or its metabolite. There were no unexpected effects of rifampicin on the short-term antiviral effect or safety of the administered antiretroviral treatment. The pharmacokinetics of enfuvirtide are not induced by a 10-day pretreatment with rifampicin.