A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism

To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of proton pump inhibitors (PPIs).

CYP2C19 2, 3, 4, 5, 6 and 17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/2, 2 wt/17, 2 2/17 and 1 2/2 were included in a randomized investigator-blinded crossover study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-hour pH monitoring was performed on days 0, 1 and 5 of oral dosing.

A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at days 1 and 5.

Esomeprazole provides acid inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.

Pharmaceutisch Weekblad
Erasmus MC: University Medical Center Rotterdam

Hunfeld, N., Touw, D., Mathot, R., Mulder, P., van Schaik, R., Kuipers, E., … Geus, W. P. (2012). Vergelijking van de zuurremmende effecten van esomeprazol en pantoprazol in relatie tot farmacokinetiek en CYP2C19-polymorfisme. Pharmaceutisch Weekblad, 147(50), 198–202. Retrieved from http://hdl.handle.net/1765/87434