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Titolo:
Menstrual cycle variability in midazolam pharmacokinetics
Autore:
Kharasch, ED; Mautz, D; Senn, T; Lentz, G; Cox, K;
Indirizzi:
Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 t Anesthesiol, Seattle, WA 98195 USA Univ Washington, Dept Med Chem, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 Dept Med Chem, Seattle, WA 98195 USA Univ Washington, Dept Obstet Gynecol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 bstet Gynecol, Seattle, WA 98195 USA Puget Sound Vet Affairs Hlth Care Syst, Anesthesiol Serv, Seattle, WA USA Puget Sound Vet Affairs Hlth Care Syst Seattle WA USA v, Seattle, WA USA
Titolo Testata:
JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 3, volume: 39, anno: 1999,
pagine: 275 - 280
SICI:
0091-2700(199903)39:3<275:MCVIMP>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ERYTHROMYCIN BREATH TEST; IN-VIVO PROBES; CYTOCHROME-P450 3A4; ALFENTANIL PHARMACOKINETICS; LIVER-MICROSOMES; CYP3A ACTIVITY; METABOLISM; GENDER; IDENTIFICATION; CLEARANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Kharasch, ED Univ Washington, Dept Anesthesiol, Box 356540, Seattle, WA 98195 USA Univ Washington Box 356540 Seattle WA USA 98195 WA 98195 USA
Citazione:
E.D. Kharasch et al., "Menstrual cycle variability in midazolam pharmacokinetics", J CLIN PHAR, 39(3), 1999, pp. 275-280

Abstract

Activity of cytochrome P450 3A4 (CYP3A4), the most abundant human P450 isoform and responsible for metabolizing approximately half of all therapeuticagents, has been speculated to vary during the menstrual cycle. This investigation evaluated CYP3A4 activity during the menstrual cycle, using midazolam clearance as a metabolic probe. Midazolam (1 mg IV) was administered tononsmoking, nonpregnant female volunteers (N = 11, age 26 +/- 5 years) with normal menstrual cycles on three separate occasions during the same cycle: days 2 (menstrual phase), 13 (estradiol peak), and 21 (progesterone peak). Venous plasma midazolam concentrations were determined by gas chromatography-mass spectrometry. Midazolam clearance was determined by noncompartmental and compartmental analysis. Midazolam plasma disposition did not differ between phases of the menstrual cycle. There was no significant difference in any measure of midazolam clearance. Noncompartmental clearances (mean +/- SD) were 7.36 +/- 2.73, 6.34 +/- 3.58, and 6.23 +/- 2.04 ml/kg/min, respectively, on days 2, 13, and 21 of the menstrual cycle. These results suggest no difference in hepatic CYP3A4 activity on menstrual cycle days 2, 13, and 21. Consideration of menstrual cycle variability in the metabolism of CYP3A4 substrates does not appear indicated in the dosing or design of clinical trials. Journal of Clinical Pharmacology 1999;39:275-280 (C) 1999 the American College of Clinical pharmacology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 09:55:21