1. ¹Clinical Pharmacology, Pfizer Global R&D, San Diego, California, USA
2. ²Biostatistics, Pfizer Global R&D, San Diego, California, USA

Correspondence: N Sarapa, E-mail: nenadsarapa@yahoo.com

³Current address: Daiichi Sankyo Pharma Development, Edison, New Jersey, USA.

Received 16 November 2006; Accepted 14 May 2007; Published online 20 June 2007.

Abstract

To assess the QTc prolongation by ritonavir (RTV) 100 mg and explore its potential use as CYP3A inhibitor in thorough QTc (TQT) studies. Randomized, crossover study of single-dose RTV 100 mg, placebo, and moxifloxacin (MFLX) 400 mg in 65 healthy subjects with serial triplicate electrocardiograms obtained for 12 h post-dose. Largest mean placebo-adjusted QTcF increase from baseline (90% confidence interval (CI)) for RTV 100 mg was noninferior to placebo (0.16 ms (-1.38, 1.69)). Study sensitivity was validated by detecting the largest mean placebo-adjusted QTcF increase from baseline (90% CI) for MFLX of 8.31 ms (6.44, 10.18). A single dose of RTV 100 mg does not cause QTc prolongation in healthy subjects. Based on the potent CYP3A4 inhibition, lack of QTc effect and better safety profile, RTV 100 mg could replace ketoconazole as the CYP3A4 inhibitor in TQT studies.