Omeprazole was dosed on days 1–7, rosiglitazone on day 11, IPE on days 12–29, omeprazole on days 19–25, and rosiglitazone on day 29. Omeprazole PK parameters were determined on days 7 and 25 (without and with IPE, respectively). This report focuses
only on the portion of the study that investigated omeprazole without and with IPE (days 1–7 and 12–25, respectively). Selleck Liproxstatin-1 The results of the rosiglitazone portion of the study will be reported separately. Because of the crossover design, the number of patients in the group that received omeprazole was the same as in the group that received omeprazole and IPE. In healthy subjects, the elimination half-life of omeprazole is 0.5–1 h . Omeprazole PK are nonlinear, with an increase in systemic availability after doses >40 mg or prolonged administration because of the effects of omeprazole on gastric pH and a saturable gastrointestinal first-pass effect [8, 13]. The bioavailability of omeprazole increases slightly with repeated doses . Therefore, to decrease variability and to maximize systemic exposure comparable to the clinical use of omeprazole, find more omeprazole
40 mg was dosed for 7 days in the current study. PK sampling was conducted over a 24-h period because of the short elimination half-life of omeprazole. Omeprazole was provided as Prilosec® 40-mg delayed-release capsules (AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA), which were Temozolomide cell line dispensed in two separate bottles for dosing on days 1–7 and days 6-phosphogluconolactonase 19–25. Omeprazole was taken once daily 1 h prior to the start of breakfast. IPE 4 g/day, the FDA-approved daily dose , was administered as two liquid-filled, 1-g gelatin capsules twice daily with or following the morning and evening meals on days 12–29. Treatments were self-administered when subjects were away from the study site, and administered by study personnel during scheduled visits. Compliance for at-home dosing was determined by study personnel by counting unused capsules and reconciling against subject diaries. Compliance was calculated as 100 × the
number of used capsules/total dosing days × 1 for omeprazole (one capsule once daily) and × 4 for IPE (two capsules twice daily). The protocol was approved by an institutional review board (IntegReview Ethics Review Board, Austin, TX, USA) and the study was conducted between February 3, 2011 and March 21, 2011 at Frontage Clinical Services (a wholly owned subsidiary of Frontage Laboratories, Hackensack, NJ, USA). The study complied with the ethical principles of Good Clinical Practice and was conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent prior to study entry. 2.3 Pharmacokinetic Sampling and Bioanalytical Methods For determination of omeprazole plasma concentrations, blood samples (6 mL) were collected prior to the day 1 dose and on days 7 and 25 at time 0 (prior to dosing) and at 0.33, 0.67, 1, 1.5, 2, 2.