This article reviews the pharmacokinetics of esomeprazole, the (S)-isomer of the proton pump inhibitor (PPI) omeprazole. Esomeprazole is the first single isomer PPI developed for the treatment of patients with acid-related diseases.
In vitro experiments in human liver microsomes demonstrated that the formation of the hydroxy and 5-O-desmethyl metabolites of esomeprazole is via cytochrome P450 (CYP) 2C19, whereas that of the sulphone metabolite is via CYP3A4. The formation rate of the hydroxy metabolite from esomeprazole is lower than for (R)-omeprazole, but that of the 2 other metabolites is higher, demonstrating stereoselective metabolism. The sum of the intrinsic clearances of all 3 metabolites for esomeprazole was one-third of that for (R)-omeprazole, suggesting lower clearance of esomeprazole in vivo.
In vivo investigations demonstrated that esomeprazole is chirally stable after administration. Esomeprazole is 97% bound to plasma proteins. In normal (extensive) metabolisers with regard to CYP2C19, esomeprazole is metabolised more slowly than omeprazole, resulting in a higher area under the concentration-time curve (AUC) after administration of the same dose. This is more pronounced after repeated administration rather than after a single dose. In poor metabolisers, the AUC is lower for esomeprazole than for omeprazole, contributing to less overall interindividual variability for esomeprazole than for omeprazole.
In general, esomeprazole and omeprazole are subject to the same metabolic transformations. Almost complete recoveries were reported and the ratio between urinary and faecal excretion is about 4: 1 for both compounds. The dose-dependent increase in AUC of esomeprazole with repeated administration results from a combination of decreased first-pass elimination and decreased systemic clearance. Patients with gastro-oesophageal reflux disease exhibit a pharmacokinetic pattern similar to that in healthy individuals, whereas elderly individuals exhibited a slightly lower metabolism rate.
Patients with a severe deficit in their liver function had a lower rate of metabolism, as would be expected, whereas those with mild to moderate liver disease did not exhibit any alteration in the pharmacokinetics. The pharmacokinetics of esomeprazole in individuals with impaired renal function is unlikely to differ from that in healthy individuals. A slight sex difference in the pharmacokinetics of esomeprazole was demonstrated in that the AUC and peak plasma drug concentration were slightly, but not statistically significantly, higher in females than in males.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Andersson T. Pharmacokinetics, metabolism and interactions of acid pump inhibitors: focus on omeprazole, lansoprazole and pantoprazole. Clin Pharmacokinet 1996; 31: 9–28
Yasuda S, Horai Y, Tomono Y, et al. Comparison of the kinetic disposition and metabolism of E3810, a new proton pump inhibitor, and omeprazole in relation to S-mephenytoin 4′-hydroxylation status. Clin Pharmacol Ther 1995; 58: 143–54
Andersson T, Holmberg J, Röhss K, et al. Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole. Br J Clin Pharmacol 1998; 45: 369–75
Äbelö A, Andersson TB, Antonsson M, et al. Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 2000; 28: 966–72
Andersson T, Bredberg E, Sunzel M, et al. Pharmacokinetics (PK) and effect on pentagastrin stimulated peak acid output (PAO) of omeprazole (O) and its 2 optical isomers, S-om-eprazole/esomeprazole (E) and R-omeprazole (R-O) [abstract]. Gastroenterology 2000; 118 (4 Pt II): A1210
Lind T, Cederberg C, Ekenved G, et al. Effect of omeprazole —a gastric proton pump inhibitor — on pentagastrin stimulated acid secretion in man. Gut 1983; 24: 270–6
Lind T, Rydberg L, Kyleback A, et al. Esomeprazole provides improved acid control vs. omeprazole in patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2000; 14: 861–7
Kahrilas PJ, Falk GW, Johnson DA, et al. Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. Aliment Pharmacol Ther 2000; 14: 1249–58
IN vitro Protein binding of omeprazole, H199/18 and H 199/19 in plasma from humans (study no. 24049). Wayne (PA): AstraZeneca, 1998 (Data on file)
Investigation of any inversion of H 199/18 in healthy male subjects (study no. SH-QBE-0027). Wayne (PA): AstraZeneca, 1998 (Data on file)
Pharmacokinetics and metabolic pattern of H 199/18 compared with omeprazole after single oral administration (study no. SH-QBE-0024). Wayne (PA): AstraZeneca, 1998 (Data on file)
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
Andersson T, Rohss K, Hassan-Alin M, et al. Pharmacokinetics (PK) and dose-response relationship of esomeprazole (E) [study no. SH-QBE-0002] [abstract]. Gastroenterology 2000; 118 (4 Pt II): A1210
Naesdal J, Andersson T, Bodemar G, et al. Pharmacokinetics of [14C]omeprazole in patients with impaired renal function. Clin Pharmacol Ther 1986; 40(3): 344–51
Hasselgren G, Hassan-Alin M, Andersson T, et al. Esomeprazole pharmacokinetics are not affected by age: an assessment in the elderly. Clin Pharmacokinet 2001; 40: 145–50
Sjovall H, Hagman I, Holmberg J, et al. Pharmacokinetics of esomeprazole in patients with liver cirrhosis [abstract]. Gastroentrology 2000; 118: A346
Effect of weight, age, gender and use of oral contraceptives on AUC and Cmax of H 199/18 (study no. AH-28602). Wayne (PA): AstraZeneca, 1999 (Data on file)
Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs 1995; 50(2): 222–39
A bioequivalence study with 40mg H 199/18 comparing a new tablet formulation with a capsule formulation in healthy subjects (study no. SH-QBE-0035). Wayne (PA): AstraZeneca, 1998 (Data on file)
Andersson T, Miners JO, Veronese M, et al. Identification of human liver cytochrome P450 isoforms mediating secondary omeprazole metabolism. Br J Clin Pharmacol 1994; 37: 597–604
All studies were sponsored by AstraZeneca.
About this article
Cite this article
Andersson, T., Hassan-Alin, M., Hasselgren, G. et al. Pharmacokinetic Studies with Esomeprazole, the (S)-Isomer of Omeprazole. Clin Pharmacokinet 40, 411–426 (2001). https://doi.org/10.2165/00003088-200140060-00003
- Repeated Dose
- Repeated Administration
- Human Liver Microsome