T Andersson1, K Röhss, E Bredberg, M Hassan-Alin. 1. Clinical Pharmacology, AstraZeneca LP, 725 Chesterbrook Blvd., Wayne, PA 19087-5677, USA. tommy.andersson@astrazeneca.com
Abstract
BACKGROUND:Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases. AIM: To examine the pharmacokinetics and pharmacodynamics of esomeprazole. METHODS: In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5. RESULTS: The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5). CONCLUSIONS: The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.
RCT Entities:
BACKGROUND:Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor developed as a single isomer for the treatment of acid-related diseases. AIM: To examine the pharmacokinetics and pharmacodynamics of esomeprazole. METHODS: In a crossover study, 12 healthy males received 5, 10 or 20 mg of esomeprazole, or 20 mg of omeprazole, once daily over 5 days. The pharmacokinetics and effects on pentagastrin-stimulated peak acid output of esomeprazole and omeprazole were studied on days 1 and 5. RESULTS: The area under the curve (AUC) of both esomeprazole and omeprazole increased from day 1 to day 5. The correlation between acid inhibition and AUC for esomeprazole could be well described with a sigmoid Emax model. The mean inhibition values of the pentagastrin-stimulated peak acid output on day 1 for 5, 10 and 20 mg of esomeprazole were 15%, 29% and 46%, respectively; the corresponding day 5 values were 28%, 62% and 90%. The mean inhibition values of the pentagastrin-stimulated peak acid output for omeprazole were 35% (day 1) to 79% (day 5). CONCLUSIONS: The pharmacokinetics of esomeprazole are time and dose dependent. There was a good correlation between AUC and effect for esomeprazole. These data suggest an increased acid inhibitory effect of esomeprazole compared to omeprazole.
Authors: Vijaya S Pratha; Daniel L Hogan; James R Lane; Paul J Williams; Michael S Burton; Richard B Lynn; Robyn G Karlstadt Journal: Dig Dis Sci Date: 2006-01 Impact factor: 3.199