Pharmacokinetics and Safety of Saquinavir/Ritonavir and Omeprazole in HIV‐infected Subjects

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. Clinical Pharmacology & Therapeutics (2008); 83 , 6, 867–872 doi: 10.1038/sj.clpt.6100375