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Titolo:
Relationship of paroxetine disposition to metoprolol metabolic ratio and CPsi P2D6*10 genotype of Korean subjects
Autore:
Yoon, YR; Cha, IJ; Shon, JH; Lim, KA; Cha, YN; Jang, IJ; Park, CW; Shin, SG; Flockhart, DA; Shin, JG;
Indirizzi:
Inje Univ, Coll Med, Dept Pharmacol, Pusan 614735, South Korea Inje Univ Pusan South Korea 614735 Pharmacol, Pusan 614735, South Korea Pusan Paik Hosp, Clin Pharmacol Ctr, Pusan, South Korea Pusan Paik Hosp Pusan South Korea lin Pharmacol Ctr, Pusan, South Korea Inha Univ, Coll Med, Dept Pharmacol, Inchon, South Korea Inha Univ Inchon South Korea l Med, Dept Pharmacol, Inchon, South Korea Seoul Natl Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Seoul Natl Univ Seoul South Korea d, Dept Pharmacol, Seoul, South Korea Georgetown Univ, Med Ctr, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 5, volume: 67, anno: 2000,
pagine: 567 - 576
SICI:
0009-9236(200005)67:5<567:ROPDTM>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPARTEINE OXIDATION POLYMORPHISM; DIFFERENT CYP2D6 GENOTYPES; CHINESE SUBJECTS; IN-VIVO; DEBRISOQUINE HYDROXYLATION; JAPANESE POPULATION; MEPHENYTOIN HYDROXYLATION; PLASMA-CONCENTRATIONS; GENETIC-ANALYSIS; S-MEPHENYTOIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Shin, JG Inje Univ, Coll Med, Dept Pharmacol, 633-165 Kaekum Dong,Jin Ku, Pusan 614735, South Korea Inje Univ 633-165 Kaekum Dong,Jin Ku Pusan SouthKorea 614735 ea
Citazione:
Y.R. Yoon et al., "Relationship of paroxetine disposition to metoprolol metabolic ratio and CPsi P2D6*10 genotype of Korean subjects", CLIN PHARM, 67(5), 2000, pp. 567-576

Abstract

Objective: To evaluate the relationship between the metabolic ratio (MR) of metoprolol, CYP2D6*10B genotype, and the disposition of paroxetine in Korean subjects. Methods: A single 40-mg dose of paroxetine was administered orally to one poor metabolizer and 15 healthy subjects recruited from 223 Korean extensive metabolizers whose phenotypes were predetermined by use of the metoprololMR. Genotypes were determined by allele-specific polymerase chain reactionand the GeneChip microarray technique. Pharmacokinetic parameters were estimated from plasma concentrations of paroxetine for more than 240 hours after the oral dose. Results: The oral clearance and area under the plasma concentration versustime curve (AUC) of paroxetine were best described by a nonlinear relationship with metoprolol MR at correlation coefficients of 0.82 and 0.91, respectively (P <.05). Nine extensive metabolizer who were either homozygous or heterozygous for CYP2D6*10B had significantly lower oral clearance values of paroxetine than six extensive metabolizers with CYP2D6*1/*1. The AUC of paroxetine in subjects who were homozygous for CYP2D6*10B (666.4 +/- 169.4 ng/mL . h) was significantly greater than that of subjects who were homozygous for the wild type (194.5 +/- 55.9 ng/mL h). Unexpectedly, the average AUC of subjects who were heterozygous for CYP2D6*10B was greater with wide variation (789.8 +/- 816.9 ng/mI, h) than that of subjects who were homozygous CYP2D6*10B/*10B mainly because of two atypical subjects whose metoprolol IC IR was not associated with the CYP2D6*10B genotype and who showed greater AUC and lower oral clearance than subjects with homozygous CYP2D6*10B. Conclusions: The CYP2D6 activity measured by metoprolol MR was a strong predictor of paroxetine disposition in Korean extensive metabolizers. In general, the extensive metabolizers with the CYP2D6*10B allele seemed to have higher plasma concentrations of paroxetine than extensive metabolizers with the wild-type CYP2D6 genotype. However, quantitative prediction of paroxetine disposition from the CYP2D6*10B genotype alone was not perfect because several Korean extensive metabolizers had metoprolol MRs that were not associated with the genotype.

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Documento generato il 27/01/20 alle ore 18:03:32