Pharmacokinetic Study of Esomeprazole in the Elderly

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Abstract
Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of patients with acid-related diseases. The aim of this study was to examine the pharmacokinetics and tolerability of esomeprazole in the elderly, relative to middle-aged patients with gastro-oesopha-geal reflux disease (GORD). Nonblinded single-centre pharmacokinetic study with historical control group. 14 healthy elderly volunteers [mean age 74 (range 71 to 80) years]. Participants received treatment with esomeprazole 40mg once daily for 5 days, with 24-hour blood sampling on days 1 and 5. The total area under the plasma concentration-time curve (AUC∞), maximum plasma drug concentration (Cmax), terminal elimination half-life (t1/2z) and time to Cmax (tmax) were determined for the parent drug and its hydroxy and sulphone metabolites. AUC∞ and Cmax data were compared with those in an historical group of 36 middle-aged patients [mean age 45 (range 29 to 58) years] with GORD, treated with an identical dosage of esomeprazole for 5 days. A total of 13 volunteers completed the study. On day 5, the mean plasma AUC∞ of esomeprazole was 16.0 µmol · h/L, Cmaxwas 5.6 µmol/L, tmax was 1.5 hours and t1/2z was 1.7 hours. The AUC∞ and Cmax values for the parent drug were 2- and 1.5-fold higher on day 5 compared with day 1. AUC∞ and Cmax values for the sulphone metabolite increased to a slightly greater extent, and values for the hydroxy metabolite were unchanged. Ratios of the AUC∞ and Cmax values between elderly volunteers and patients with GORD were 1.25 [95% confidence interval (CI) 0.94, 1.67] and 1.18 (0.91, 1.52), respectively. Esomeprazole was well tolerated and there were no safety concerns. The AUC∞ and Cmax values in the elderly were not significantly different from those obtained in a group of middle-aged patients. The difference for AUC∞ was 25% (95% CI −6% to +67%). Esomeprazole has a wide therapeutic window and our results do not indicate that dosage adjustment should be necessary in the elderly.