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Titolo:
EFFECTS OF GENETICALLY-DETERMINED S-MEPHENYTOIN 4-HYDROXYLATION STATUS AND CIGARETTE-SMOKING ON THE SINGLE-DOSE PHARMACOKINETICS OF ORAL ALPRAZOLAM
Autore:
OTANI K; YASUI N; KANEKO S; OHKUBO T; OSANAI T; SUGAWARA K; HAYASHI K; CHIBA K; ISHIZAKI T;
Indirizzi:
HIROSAKI UNIV HOSP,DEPT NEUROPSYCHIAT,HON CHO 53 HIROSAKI AOMORI 036 JAPAN HIROSAKI UNIV HOSP,DEPT PHARM HIROSAKI AOMORI 036 JAPAN GOSHOGAWARA CITY HOSP,DEPT PHARM GOSHOGAWARA JAPAN YAMANOUCHI PHARMACEUT CO LTD,DEPT BIOSTAT TOKYO JAPAN INT MED CTR JAPAN,DEPT CLIN PHARMACOL TOKYO JAPAN
Titolo Testata:
Neuropsychopharmacology
fascicolo: 1, volume: 16, anno: 1997,
pagine: 8 - 14
SICI:
0893-133X(1997)16:1<8:EOGS4S>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; REUPTAKE-INHIBITOR ANTIDEPRESSANTS; POOR METABOLIZERS; ORIENTAL SUBJECTS; IN-VITRO; HYDROXYLATION; OMEPRAZOLE; DIAZEPAM; 4'-HYDROXYLATION; FLUVOXAMINE;
Keywords:
ALPRAZOLAM; METABOLISM; S-MEPHENYTOIN 4-HYDROXYLATION; SMOKING; CYTOCHROME P450 (CYP) ISOFORMS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
K. Otani et al., "EFFECTS OF GENETICALLY-DETERMINED S-MEPHENYTOIN 4-HYDROXYLATION STATUS AND CIGARETTE-SMOKING ON THE SINGLE-DOSE PHARMACOKINETICS OF ORAL ALPRAZOLAM", Neuropsychopharmacology, 16(1), 1997, pp. 8-14

Abstract

This study examines the effects of genetically determined S-mephenytoin 4-hydroxylation capacity and cigarette smoking on the single-dose pharmacokinetics of oral alprazolam in 12 healthy male volunteers. Six subjects each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Seven subjects were smokers (>10 cigarettes/day), and five were nonsmokers, according to their self-reports. Each subject took a single oral close of 0.8 mg of alprazolam, and blood samples were collected up to 48 hours postdose. Psychomotor function was assessed at times of blood samplings using the Digit Symbol Substitution Test (DSST), Visual Analog Scale (VAS), and UKU SideEffect Rating Scale. Plasma alprazolam concentrations were measured by a high-performance liquid chromatography assay. None of the mean pharmacokinetic parameters was significantly different between the EM andPM phenotype groups. Although the mean elimination half-life was significantly shorter in the smoker group (p < .01) than in the nonsmoker group (13.1 +/- 2.9 vs. 20.0 +/- 2.7 hours, mean +/- SD), other pharmacokinetic parameters did not differ significantly between the two groups. Psychomotor function parameters did not differ significantly either between the EM and PM groups or between the nonsmoker and smoker groups. The present study thus suggests that neither S-mephenytoin 4-hydroxylation status nor self-reports of extensive cigarette smoking has amajor impact on the metabolism of alprazolam in humans.

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Documento generato il 19/01/20 alle ore 20:22:47