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Titolo:
P-hydroxylation of phenobarbital: Relationship to (s)-mephenytoin hydroxylation (CYP2C19) polymorphism
Autore:
Hadama, A; Ieiri, I; Morita, T; Kimura, M; Urae, A; Irie, S; Kaneda, T; Mamiya, K; Tashiro, N; Higuchi, S; Otsubo, K;
Indirizzi:
Tottori Univ, Fac Med, Dept Hosp Pharm, Yonago, Tottori 6838504, Japan Tottori Univ Yonago Tottori Japan 6838504 Yonago, Tottori 6838504, Japan Kyushu Univ, Grad Sch, Dept Clin Pharmacokinet, Div Pharmaceut Sci, Fukuoka, Japan Kyushu Univ Fukuoka Japan macokinet, Div Pharmaceut Sci, Fukuoka, Japan Kyushu Univ, Fac Med, Dept Neuropsychiat, Fukuoka 812, Japan Kyushu Univ Fukuoka Japan 812 ed, Dept Neuropsychiat, Fukuoka 812, Japan
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 2, volume: 23, anno: 2001,
pagine: 115 - 118
SICI:
0163-4356(200104)23:2<115:POPRT(>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
S-MEPHENYTOIN; GENETIC-POLYMORPHISM; INDUCTION; PHARMACOKINETICS; POPULATIONS; METABOLISM; OMEPRAZOLE; RIFAMPICIN; FELBAMATE;
Keywords:
phenobarbital; p-hydroxylation; genetic polymorphism; CYP2C19;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Ieiri, I Tottori Univ, Fac Med, Dept Hosp Pharm, Nishi Machi 36-1, Yonago,Tottori 6838504, Japan Tottori Univ Nishi Machi 36-1 Yonago Tottori Japan 6838504 Japan
Citazione:
A. Hadama et al., "P-hydroxylation of phenobarbital: Relationship to (s)-mephenytoin hydroxylation (CYP2C19) polymorphism", THER DRUG M, 23(2), 2001, pp. 115-118

Abstract

The aim of the current study was to compare the pharmacokinetics of phenobarbital (PB) in extensive metabolizers (EMs) and poor metabolizers (PMs) ofS-mephenytoin. Ten healthy volunteers (5 EMs and 5 PMs) were given 30 mg PB daily for 14 days. PB and p-hydroxyphenobarbital (p-OHPB) in serum and urine were measured by high-performance liquid chromatography (HPLC). Urinaryexcretion (12.5% versus 7.7%) and formation clearance (29.8 versus 21.1 mL/h) of p-OHPB, one of the main metabolites of PB, were significantly lower (p < .05) in PMs than in EMs. However, area under the serum concentration-time curve (153.3 in the EMs versus 122.9 <mu>g.h/mL in the PMs), total (210.8 versus 254.9 mL/h) and renal clearance (53.1 versus 66.1 mL/h) of PB were identical between the two groups. To compare the inducibility of CYP2C19,mephenytoin was also given prior to and on the last day of PB treatment. The urinary level of 4 ' -hydroxymephenytoin was analyzed by a validated gaschromatograpy/mass spectrometry (GC/MS) method. The mephenytoin hydroxylation index did not change in either EMs (1.42 versus 1.42) or PMs (341.4 versus 403.5), showing that CYP2C19 was not induced by treatment with PB. These results indicated that the p-hydroxylation pathway of PB co-segregates with the CYP2C19 metabolic polymorphism. However, the overall disposition kinetics of PB were not different between EMs and PMs, and therefore polymorphic CYP2C19 seems have no major clinical implications.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 10:31:30