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-oesophageal 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 40 mg once daily for 5 days, with 24-hour blood sampling on days 1 and 5. The total area under the plasma concentration-time curve (AUCinfinity), maximum plasma drug concentration (Cmax), terminal elimination half-life (t(1/2z)) and time to Cmax (tmax) were determined for the parent drug and its hydroxy and sulphone metabolites. AUCinfinity 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 AUCinfinity of esomeprazole was 16.0 micromol x h/L, Cmax was 5.6 micromol/L, tmax was 1.5 hours and t(1/2z) was 1.7 hours. The AUCinfinity and Cmax values for the parent drug were 2- and 1.5-fold higher on day 5 compared with day 1. AUCinfinity and Cmax values for the sulphone metabolite increased to a slightly greater extent, and values for the hydroxy metabolite were unchanged. Ratios of the AUCinfinity 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 AUCinfinity and Cmax values in the elderly were not significantly different from those obtained in a group of middle-aged patients. The difference for AUCinfinity 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.
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-oesophageal 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 40 mg once daily for 5 days, with 24-hour blood sampling on days 1 and 5. The total area under the plasma concentration-time curve (AUCinfinity), maximum plasma drug concentration (Cmax), terminal elimination half-life (t(1/2z)) and time to Cmax (tmax) were determined for the parent drug and its hydroxy and sulphone metabolites. AUCinfinity 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 AUCinfinity of esomeprazole was 16.0 micromol x h/L, Cmax was 5.6 micromol/L, tmax was 1.5 hours and t(1/2z) was 1.7 hours. The AUCinfinity and Cmax values for the parent drug were 2- and 1.5-fold higher on day 5 compared with day 1. AUCinfinity and Cmax values for the sulphone metabolite increased to a slightly greater extent, and values for the hydroxy metabolite were unchanged. Ratios of the AUCinfinity 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 AUCinfinity and Cmax values in the elderly were not significantly different from those obtained in a group of middle-aged patients. The difference for AUCinfinity 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.
Authors: S Landahl; T Andersson; M Larsson; B Lernfeldt; P Lundborg; C G Regårdh; E Sixt; I Skånberg Journal: Clin Pharmacokinet Date: 1992-12 Impact factor: 6.447
Authors: M S Ching; G W Mihaly; P W Angus; D J Morgan; S Devenish-Meares; N D Yeomans; R A Smallwood Journal: Br J Clin Pharmacol Date: 1991-02 Impact factor: 4.335
Authors: T Andersson; J O Miners; M E Veronese; W Tassaneeyakul; W Tassaneeyakul; U A Meyer; D J Birkett Journal: Br J Clin Pharmacol Date: 1993-12 Impact factor: 4.335
Authors: Kate McKeage; Stephanie K A Blick; Jamie D Croxtall; Katherine A Lyseng-Williamson; Gillian M Keating Journal: Drugs Date: 2008 Impact factor: 9.546