Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
High-dose omeprazole: Use of a multiple-dose study design to assess bioequivalence and accuracy of CYP2C19 phenotyping
Autore:
Kovacs, P; Edwards, DJ; Lalka, D; Scheiwe, WM; Stoeckel, K;
Indirizzi:
Wayne State Univ, Dept Pharm Practice, Detroit, MI 48202 USA Wayne State Univ Detroit MI USA 48202 arm Practice, Detroit, MI 48202 USA Debrecen Univ Med, Dept Med, H-4012 Debrecen, Hungary Debrecen Univ Med Debrecen Hungary H-4012 Med, H-4012 Debrecen, Hungary W Virginia Univ, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA W Virginia Univ Morgantown WV USA 26506 eut Sci, Morgantown, WV 26506 USA Mepha Ltd, Aesch, Switzerland Mepha Ltd Aesch SwitzerlandMepha Ltd, Aesch, Switzerland ClinPharm Support, Basel, Switzerland ClinPharm Support Basel Switzerland inPharm Support, Basel, Switzerland
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 5, volume: 21, anno: 1999,
pagine: 526 - 531
SICI:
0163-4356(199910)21:5<526:HOUOAM>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
S-MEPHENYTOIN 4'-HYDROXYLATION; POOR METABOLIZERS; GENOTYPE; HYDROXYLATION; DISPOSITION; POPULATION; PHARMACOKINETICS; BIOAVAILABILITY; IDENTIFICATION; POLYMORPHISM;
Keywords:
omeprazole; phenotype; genotype; CYP2C19; bioequivalence;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Edwards, DJ Wayne State Univ, Dept Pharm Practice, Detroit, MI 48202 USA Wayne State Univ Detroit MI USA 48202 , Detroit, MI 48202 USA
Citazione:
P. Kovacs et al., "High-dose omeprazole: Use of a multiple-dose study design to assess bioequivalence and accuracy of CYP2C19 phenotyping", THER DRUG M, 21(5), 1999, pp. 526-531

Abstract

The objectives of this multiple-dose study were to compare the performanceof a new formulation of omeprazole (40 mg) with that of an established formulation and to assess the accuracy of CYP2C19 phenotyping during high-dosechronic administration. Twenty-eight healthy subjects were randomized (1:1) to receive 40 mg of either Gasec-40 Gastrocaps (Mepha) or Antra 40 (Astra) daily for 5 days. The pharmacokinetics of omeprazole and the omeprazole/5'-hydroxyomeprazole ratio 3 hours postdose were assessed on day 5. Subjectsswitched formulations starting on day 6, and all measurements were repeated on day 8, Subjects with metabolic ratios greater than 6 were genotyped for CYP2C19. Gasec-40 was round to be bioequivalent to Antra based on the 90%confidence interval for AUC (102.4-111.7) and C-max (100.6 - 120.7). Formulation had no effect on the ratio of omeprazole to 5'-hydroxyomeprazole, which was higher than previously reported with single 20 mg doses of omeprazole. The mean ratio did not differ between day 5 and day 8 but was highly variable: 7 of 28 subjects had more than a 2-fold difference between assessments. In four individuals identified by genotype as extensive metabolizers (EMs), phenotype could not be clearly assigned. The relative bioavailabilityof omeprazole can be accurately assessed using this multiple-dose study design. Chronic administration of 40 mg doses of omeprazole shifts the metabolic ratio in EMs toward that in poor metabolizers (PMs), apparently becauseof the nonlinear metabolic clearance of the drug. The assignment of phenotype in patients receiving chronic high-dose omeprazole treatment should be interpreted with caution.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 12:27:20