Pharmacokinetics and pharmacodynamics of esomeprazole, the S-isomer of omeprazole.
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.


OBJECTIVE
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.
Andersson
T
T
Clinical Pharmacology, AstraZeneca LP, 725 Chesterbrook Blvd., Wayne, PA 19087-5677, USA. tommy.andersson@astrazeneca.com
Röhss
K
K
Bredberg
E
E
Hassan-Alin
M
M
D000284:Administration, Oral; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D064098:Esomeprazole; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010418:Pentagastrin / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000097:blood / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013997:Time Factors
D000897:Anti-Ulcer Agents; D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D010418:Pentagastrin; D009853:Omeprazole; D064098:Esomeprazole