Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects.
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 impa...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 64; no. 12; pp. 1175 - 1180 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Dec2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105597901&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105597901 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Dec2008 vid: 64 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 105597901 2010135376 10.1007/s00228-008-0529-z NLM18654768 105597901 ppf: 1175 ppct: 5 formats: fmt: @attributes: type: P tig: atl: Kinetics of omeprazole and escitalopram in relation to the CYP2C19*17 allele in healthy subjects. aug: au: Rosenborg SO Mwinyi J Andersson M Baldwin RM Pedersen RS Sim SC Bertilsson L Ingelman-Sundberg M Eliasson E affil: Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden. staffan.ohlsson@ki.se sug: subj: Alleles Enzymes Pharmacokinetics Omeprazole Pharmacokinetics Serotonin Uptake Inhibitors Therapeutic Use Adult Europe Female Fisher's Exact Test Funding Source Male Mann-Whitney U Test Omeprazole Administration and Dosage Omeprazole Blood Pharmacy and Pharmacology Serotonin Uptake Inhibitors Adverse Effects Serotonin Uptake Inhibitors Blood Serotonin Uptake Inhibitors Metabolism T-Tests Volunteer Workers Human Adult: 19-44 years Female Male ab: 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 (AUC(0-12h)) 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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