CLINICAL PHARMACOLOGY Pharmacokinetics Absorption NEXIUM Delayed-Release Capsules contain an enteric-coated pellet formulation of esomeprazole magnesium. After oral administration peak plasma levels (Cmax) occur at approximately 1.5 hours (Tmax). The Cmax increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 µmol* hr/ L on day 1 to 11.2 µmol* hr/ L on day 5 after 40 mg once daily dosing. The AUC after administration of a single 40 mg dose of esomeprazole is decreased by 43-53% after food intake compared to fasting condi-tions. Esomeprazole should be taken at least one hour before meals. The pharmacokinetic profile of esomeprazole was determined in 36 patients with symptomatic gastroesophageal reflux disease following repeated once daily administration of 20 mg and 40 mg capsules of NEXIUM over a period of five days. The results are shown in the following table: Pharmacokinetic Parameters of NEXIUM Following Oral Dosing for 5 Days Parameter NEXIUM NEXIUM 40 mg 20 mg AUC (µmol* h/ L) 12.6 4.2 Coefficient of variation 42% 59% Cmax (µmol/ L) 4.7 2.1 Tmax (h) 1.6 1.6 t1/ 2 (h) 1.5 1.2 Values represent the geometric mean, except the Tmax, which is the arithmetic mean. Distribution Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2-20 µmol/ L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L. | ||||
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