Omeprazole
Omeprazole. Irreversible H+/K+-ATPase inhibitor — covalently binds activated proton pumps in gastric parietal cells. CYP2C19 substrate (poor… Oral half-life 0.6 h.
Irreversible H+/K+-ATPase inhibitor — covalently binds activated proton pumps in gastric parietal cells. CYP2C19 substrate (poor metabolizers have 5× higher AUC); also moderate CYP2C19 inhibitor (lowers clopidogrel activation).
PK re-sourced wholesale to Regardh 1990 (PMID:2315973), 8 young healthy subjects given 10 mg intravenously and 20 mg orally: verbatim "Mean Vss was 0.23 +/- 0.04 L/kg" (16.1 L at 70 kg, a TRUE volume), "The median bioavailability was 39% (25-117%)", and "t1/2 for the i.v. dose was 35 min (16-150 min) and 39 min (14-186 min) after oral administration" — the two agreeing, so one disposition value serves both routes. The stored 12 L was pantoprazole figure. The stored 0.6 h was verbatim but is the CYP2C19 HOMOZYGOUS-EXTENSIVE-METABOLISER subgroup alone: the same abstract gives 1.1 h heterozygous and 2.8 h poor, a 4.7-fold spread with an 8-fold exposure spread, so no scalar is defensible without a genotype covariate. THE EFFECT IS DECOUPLED ABOUT FIFTEEN-FOLD AND ANY DOSING MODEL DRIVEN OFF THIS HALF-LIFE IS INVALID: binding is covalent, and in one study the same patients showed half-lives of 2.3 h against durations of action of 34 h, with acid secretion normal only after 3-4 days. ka 4 dropped: absorption is modelled zero-order WITH A LAG measured at 0.62 h, a property of the enteric coat.
Pharmacokinetics
- Oral — t½ 35 min · F 39% · Vd 16.1 L
- IV — t½ 35 min · F 100% · Vd 16.1 L
Related compounds
- Clopidogrel — caution
Sources: PMID:2315973, PMID:2044903