1. ¹St Stephen's Centre, Chelsea and Westminster NHS Foundation Trust, London, UK
2. ²University of Liverpool, Liverpool, UK
3. ³Roche, Welwyn, UK

Correspondence: M Boffito, (marta.boffito@chelwest.nhs.uk)

Received 5 February 2007; Accepted 13 June 2007; Published online 26 September 2007.

Abstract

We investigated the pharmacokinetics and safety of saquinavir/ritonavir when administered with omeprazole simultaneously and 2 h apart to human immunodeficiency virus (HIV) subjects. Saquinavir/ritonavir 12-h pharmacokinetics was assessed with and without omeprazole 40 mg. Subjects were randomized to group A (saquinavir/ritonavir and omeprazole simultaneously/2 h apart) or group B (saquinavir/ritonavir and omeprazole 2 h apart/simultaneously). Saquinavir/ritonavir pharmacokinetics was assessed on days 1, 8, and 22. Within-subject changes were evaluated by geometric mean ratios and 90% confidence interval (CI). Twelve subjects completed the study. GM (90% CI) for saquinavir area under the curve (AUC)_{0- 12} (ng h/ml), trough concentration (C_trough) (ng/ml), and maximum concentration (C_max) (ng/ml) were 14,698 (13,242–20,636), 433 (368–758), 2,513 (2,243–3,329) without omeprazole; 22,646 (18,536–131,861), 750 (619–1,280), 3,890 (3,223–5,133) with omeprazole simultaneously; and 24,549 (20,884–38,894), 851 (720–1,782), 4,141 (3,554–5,992) with omeprazole 2 h earlier. Simultaneous administration of omeprazole significantly increased saquinavir AUC_{0- 12}, C_trough, and C_max by 54, 73, and 55% , whereas staggered administration by 67, 97, and 65% . No grade 3/4 toxicity or lab abnormalities were observed. In the presence of omeprazole, saquinavir plasma exposure is significantly increased in HIV-infected subjects whether administered simultaneously or 2 h apart.