The Pharmacokinetics of Omeprazole in Humans—A Study of Single Intravenous and Oral Doses

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Abstract
The pharamacokinetics of omeprazole, hydroxyomeprazole, omeprazolesulfone, and “remaining metabolites” have been studied in eight young healthy subjects following an acute i.v. and oral dose of 10 and 20 mg of 14C-labeled drug, respectively. The oral dose was given as a buffered solution. Two subjects exhibited essentially higher and more sustained plasma levels of omeprazole than the others. This was due to a higher bioavailability, lower clearance, and longer t1/2 of omeprazole in these two subjects. Maximum concentration (0.7–4.6 mUmol/L) was reached between 10 and 25 min after oral dosing. The median bioavailability was 39% (25–117%) and the median systemic plasma clearance was 624 ml/min (range of 59–828 ml/min). The corresponding t1/2 for the i.v. dose was 35 min (16–150 min) and 39 min (14–186 min) after oral administration. The drug was rapidly distributed to extravascular sites (mean t1/2Λ1 = 3.0 \pm 0.8 min). Mean Vss was 0.23 \pm 0.04 L/kg. Low systemic clearance of omeprazole was associated with a decreased formation rate of hydroxyomepraxole and “remaining metabolites” while omeprazole-sulfone formation seemed to be less affected. However, there was a clear-cut correlation between the t1/2 of omeprazole and of its omeprazolesulfone metabolite, indicating that the elimination of these two compounds is mediated by the same isoenzyme. The mean urinary recovery of the radioactive dose during 96 h was 78.3 \pm 2.3 and 75.7 \pm 2.6% for the i.v. and oral dose, respectively. Insignificant amounts were due to unchanged drug and omeprazolesulfone. The excretion of hydroxyomeprazole during the first 12 h varied between 4.6 to 15.5% of a given dose. The mean recovery of radioactivity in the feces was 19.3 \pm 3.1% of a given i.v. dose and 18.2 \pm 2.3% when given orally. It is concluded that omeprazole is mainly eliminated metabolically and that there is a substantial interindividual variation in the rate of formation of primary and secondary metabolites. This variation in omeprazole disposition is probably of limited clinical importance. The half-life, with a maximum of 3 h, is too short to cause accumulation when the drug is administered in a once-daily regimen.