Optimal dose regimens of esomeprazole for gastric acid suppression with minimal influence of the CYP2C19 polymorphism

• Published in: European journal of clinical pharmacology Vol. 65; no. 1; pp. 55 - 64
• Main Authors: Lou, Horng-Yuan, Chang, Chun-Chao, Sheu, Ming-Thau, Chen, Ying-Chen, Ho, Hsiu-O
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.01.2009; Springer Nature B.V
• Subjects: Adult; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biomedical and Life Sciences; Biomedicine; Clinical trials; Cytochrome P-450 CYP2C19; Down-Regulation; Drug Administration Schedule; Drug dosages; Esomeprazole - administration & dosage; Esomeprazole - blood; Esomeprazole - pharmacokinetics; Gastric Acid - secretion; Gastric Acidity Determination; Gastroesophageal reflux; Gastroesophageal Reflux - drug therapy; Gastroesophageal Reflux - enzymology; Gastroesophageal Reflux - genetics; Gene Frequency; Heterozygote; Homozygote; Humans; Pharmaceuticals; Pharmacogenetics; Pharmacology; Pharmacology/Toxicology; Phenotype; Pilot Projects; polymorphism; Polymorphism, Genetic; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - blood; Proton Pump Inhibitors - pharmacokinetics; Taiwan; Treatment Outcome; Young Adult; GERD; CYP2C19; Esomeprazole; Intragastric pH; Polymorphism
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-008-0552-0

Objective In this pilot study, we attempted to determine the optimal dosage regimens of esomeprazole for treatment of GERD with minimal influence of the CYP2C19 polymorphism through a study of the pharmacokinetics and pharmacodynamics of esomeprazole given at 3 different dosage regimens with the same total daily dose. Methods Each of the 3genotypes of CYP2C19 , homozygous extensive metabolizers (homEMs), heterozygous EMS (hetEMs), and poor metabolizers (PMs) were recruited in this clinical trial. Subjects were given a placebo followed by the administration of esomeprazole, at a dose of 40 mg once daily (40QD), 20 mg twice daily (20TD), or 10 mg 4 times daily (10Q4D) for 7 days. Twenty-four-hour and nocturnal intragastric pH and plasma esomeprazole concentrations were all determined on day 7. Results The pharmacokinetic parameters and dynamic characteristics differed among the 3 CYP2C19 genotype groups. With esomeprazole 40QD, gastric acid suppression was insufficient to achieve a therapeutic effect, while 20TD and 10Q4D were found to be effective in controlling both daytime and nocturnal gastric acidity for all 3 genotype groups. Conclusions It was confirmed that intragastric pH values and plasma esomeprazole concentrations potentially depended on the CYP2C19 genotype status for treatment with esomeprazole. Dosage regimens of divided doses of 20TD or 10Q4D esomeprazole yielded improved antisecretory effects with a minimal influence of CYP2C19 polymorphisms.