Thorough QT/QTc Study of Ritonavir-Boosted Saquinavir Following Multiple-Dose Administration of Therapeutic and Supratherapeutic Doses in Healthy Participants

• Autor: Zhang, Xiaoping ; Jordan, Paul ; Cristea, Laura ; Salgo, Miklos ; Farha, Rana ; Kolis, Stanley ; Lee, Lois S.
• Assuntos: Adolescent ; Adult ; Aza Compounds - adverse effects ; Confidence intervals ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Therapy, Combination ; Electrocardiography ; Female ; Fluoroquinolones ; HIV Protease Inhibitors - administration & dosage ; HIV Protease Inhibitors - adverse effects ; Humans ; Least-Squares Analysis ; Long QT Syndrome - chemically induced ; Male ; Middle Aged ; moxifloxacin ; Quinolines - adverse effects ; ritonavir ; Ritonavir - administration & dosage ; Ritonavir - adverse effects ; Saquinavir ; Saquinavir - administration & dosage ; Saquinavir - adverse effects ; thorough QT/QTc study ; Torsades de Pointes - chemically induced ; Young Adult
• É parte de: Journal of clinical pharmacology, 2012-04, Vol.52 (4), p.520-529
• Notas: istex:1EBB7D48E9E06CF0C8C02496EECEE82034F9EF60
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• Descrição: 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 (ddQTcSdense) was the primary endpoint. Greatest mean increase in ddQTcSdense 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. ddQTcBdense and ddQTcFdense were similar to ddQTcSdense. No QTcS, QTcF, or QTcB measurements were >500 ms. One participant receiving 1000/100 mg and 3 receiving 1500/100 mg had a maximum ddQTcSdense >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.
  
• Editor: Oxford, UK: Blackwell Publishing Ltd
  
• Idioma: Inglês