Phase I study of omeprazole - Single-dose and multiple-dose studies. : Single-Dose Dose and Multiple-Dose Studies

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We investigated the tolerance and pharmacokinetics of omeprazole, a new anti-ulcer drug, in single- and multiple-dose studies in healthy male volunteers. The results are summarized as follows. No abnormal findings in subjective and objective symptoms, blood pressure, heart rate, body temperature, respiratory rate, ECG, or body weight were seen in either study. In the laboratory investigations, some clinical values were outside the normal range. However, these changes were slight and not clinically relevant. Mean plasma concentrations of the drug after single doses of 10, 20, and/or 40 mg peaked at 1. 3-2. 3 hours and thereafter declined with half-lives of 1. 6-2. 8 hours. In all the dose groups, less than 1% of the given dose was excreted as unchanged in the urine, and 12-14% of the dose was excreted as the hydroxylated metabolite in the 24-hour urine. Similar plasma concentration profiles were obtained after dosing before breakfast and under fasting conditions in the single-dose study, and no food effects on the absorption of the drug were seen. In the multiple-dose study in volunteers given 20mg once a day for 7 days before or after breakfast, the time required to reach the peak concentration (Tmax) did not differ significantly between days 1 and 7, and the area under the plasma concentration curve (AUC) was greater on day 7 than on day 1. This indicates that the amount of the absorption increased after multiple dosing.