Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects
| Autor: | Sarah C. Sim, R. Michael Baldwin, Erik Eliasson, Staffan Rosenborg, Leif Bertilsson, Magnus Ingelman-Sundberg, Rasmus Steen Pedersen, Jessica Mwinyi, Maria Andersson |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype medicine.drug_class Metabolic Clearance Rate Proton-pump inhibitor CYP2C19 Pharmacology Citalopram Drug Administration Schedule Substrate Specificity Young Adult Pharmacokinetics Internal medicine medicine Escitalopram Humans Pharmacology (medical) Mephenytoin Omeprazole Alleles Chemistry General Medicine Middle Aged Anti-Ulcer Agents Cytochrome P-450 CYP2C19 Endocrinology Area Under Curve Antidepressive Agents Second-Generation Female Aryl Hydrocarbon Hydroxylases Reuptake inhibitor Pharmacogenetics medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 64(12) |
| ISSN: | 1432-1041 |
| Popis: | 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. 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. 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). 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. |
| Databáze: | OpenAIRE |
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