Abstract
Objective
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).
Design
Nonblinded single-centre pharmacokinetic study with historical control group.
Patients and Participants
14 healthy elderly volunteers [mean age 74 (range 71 to 80) years].
Methods
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.
Results
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.
Conclusions
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.
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References
Richardson P, Hawkey CJ, Stack WA. Proton pump inhibitors: pharmacology and rationale for use in gastrointestinal disorders. Drugs 1998; 56: 307–35
Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61: 331–9
Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors. Focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996; 31: 9–28
Breuel HP, Hartmann M, Bondy S, et al. Pantoprazole in the elderly: no dose-adjustment [abstract]. Gut 1994; Suppl. 4: 77
Flouvat B, Delhotal-Landes B, Cournot A, et al. Single and multiple dose pharmacokinetics of lansoprazole in elderly subjects. Br J Clin Pharmacol 1993; 36: 467–9
Landahl S, Andersson T, Larsson ME, et al. Pharmacokinetic study of omeprazole in elderly healthy volunteers. Clin Pharmacokinet 1992; 23: 469–76
Lind T, Rydberg L, Kylebäck A, et al. Esomeprazole provides improved acid control versus omeprazole in patients with symptoms of gastro-esophageal reflux disease. Aliment Pharmacol Ther 2000; 14: 861–7
Äbelö A, Andersson TB, Antonsson M, et al. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 2000; 28: 966–72
Lagerström PO, Persson BA. Determination of omeprazole and metabolites in plasma and urine by liquid chromatography. J Chromatography 1984; 309: 347–56
Hussein Z, Granneman GR, Mukherji D, et al. Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole. Br J Clin Pharmacol 1993; 36: 391–8
Laurent AL, Merritt GJ, Setoyama T, et al. Rabeprazole: pharmacokinetics and safety in the elderly. Clin Geriatr 1999; 7: 27–33
Delhotal-Landes B, Petite JP, Flouvat B. Clinical pharmacokinetics of lansoprazole. Clin Pharmacokinet 1995; 28: 458–70
Barclay ML, Begg EJ, Robson RA, et al. Lansoprazole pharmacokinetics differ in patients with esophagitis compared to healthy volunteers. Aliment Pharmacol Ther 1999; 13: 1215–9
Ching MS, Mihaly GW, Angus PW, et al. Oral bioavailability of omeprazole before and after chronic therapy in patients with duodenal ulcer. Br J Clin Pharmacol 1991; 31: 166–70
Hassan-Alin M, Andersson T, Bredberg E, et al. Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol 2000; 56: 665–70
Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. J Cardiovasc Pharmacol 1983; 5: 1093–6
Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 1977; 4: 439–48
Andersson T, Miners JO, Veronese ME, et al. Identification of human liver cytochrome P450 isoforms mediating omeprazole metabolism. Br J Clin Pharmacol 1993; 36: 521–30
Andersson T, Miners JO, Veronese ME, et al. Identification of human liver cytochrome P450 isoforms mediating secondary omeprazole metabolism. Br J Clin Pharmacol 1994; 37: 597–604
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Hasselgren, G., Hassan-Alin, M., Andersson, T. et al. Pharmacokinetic Study of Esomeprazole in the Elderly. Clin Pharmacokinet 40, 145–150 (2001). https://doi.org/10.2165/00003088-200140020-00006
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DOI: https://doi.org/10.2165/00003088-200140020-00006