Kinetics of omeprazole and escitalopram in relation to the CYP2C1917 allele in healthy subjects

• Published in: European journal of clinical pharmacology Vol. 64; no. 12; pp. 1175 - 1179
• Main Authors: Ohlsson Rosenborg, Staffan, Mwinyi, Jessica, Andersson, Maria, Baldwin, R. Michael, Pedersen, Rasmus Steen, Sim, Sarah C, Bertilsson, Leif, Ingelman-Sundberg, Magnus, Eliasson, Erik
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.12.2008; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Adult; Alleles; Anti-Ulcer Agents - blood; Anti-Ulcer Agents - pharmacokinetics; Antidepressants; Antidepressive Agents, Second-Generation - blood; Antidepressive Agents, Second-Generation - pharmacokinetics; Area Under Curve; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Citalopram - blood; Citalopram - pharmacokinetics; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Drug dosages; Drug metabolism; Female; Genotype; Genotype & phenotype; Humans; Male; Medical sciences; Metabolic Clearance Rate - genetics; Metabolism; Middle Aged; Omeprazole - blood; Omeprazole - pharmacokinetics; Pharmacogenetics; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Poor responders; Prescription drugs; Serotonin uptake inhibitor; Substrate Specificity; Therapeutic failure; Young Adult; Pharmacogenetics; Therapeutic failure; Antidepressants; Poor responders; Drug metabolism; Pharmacokinetics; Serotonin uptake inhibitor; Isozyme; Psychotropic; H; Antiulcer agent; K; Reuptake inhibitor; Proton pump inhibitor; Selective serotonin reuptake inhibitor; Antisecretory agent; Antidepressant agent; Genetics; Human; Drug; Healthy subject; Serotonin; Enzyme; Escitalopram; Cytochrome P450; Enzyme inhibitor; Metabolism; Omeprazole; Allele; Treatment; Benzimidazole derivatives; Neurotransmitter; exchanging ATPase; Hydrolases; Kinetics
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-008-0529-z

Purpose Ultrarapid drug metabolism of antidepressants has been associated with therapeutic failures. The CYP2C19*17 allele has been associated with higher levels of CYP2C19 gene transcription and increased rates of omeprazole and mephenytoin metabolism. The aim of this study was to compare the impact of the CYP2C19*17 allele on omeprazole single-dose kinetics with escitalopram exposure at steady state in volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1. Methods Sixteen healthy volunteers participated in both study parts, five homozygous for CYP2C19*17 and 11 homozygous for CYP2C19*1. Individual pharmacokinetic parameters were determined after single-dose omeprazole of 40 mg and after 1 week on escitalopram 5 mg b.i.d. Results Escitalopram area under the concentration time curve from zero to 12 h (AUC₀₋₁₂h) was 21% lower in homozygous carriers of CYP2C19*17 compared with CYP2C19*1 (p = 0.08). There was a significant correlation between escitalopram exposure at steady state and the single-dose kinetics of omeprazole (Spearman correlation coefficient of 0.67; p = 0.006). Conclusion Based on our investigation using two different CYP2C19 substrates, we concluded that a clinically significant difference in escitalopram or omeprazole kinetics between the genotypes appears unlikely.