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Titolo:
ASSESSMENT OF CYTOCHROME-P450 3A4 ACTIVITY DURING THE MENSTRUAL-CYCLEUSING ALFENTANIL AS A NONINVASIVE PROBE
Autore:
KHARASCH ED; RUSSELL M; GARTON K; LENTZ G; BOWDLE TA; COX K;
Indirizzi:
UNIV WASHINGTON,DEPT ANESTHESIOL,BOX 356540 SEATTLE WA 98195 VET AFFAIRS PUGET SOUND HLTH CARE SYST,ANESTHESIOL SERV SEATTLE WA 00000
Titolo Testata:
Anesthesiology
fascicolo: 1, volume: 87, anno: 1997,
pagine: 26 - 35
SICI:
0003-3022(1997)87:1<26:AOC3AD>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ERYTHROMYCIN BREATH TEST; CYCLOSPORINE-A OXIDASE; HUMAN-LIVER; IN-VIVO; HUMAN HEPATOCYTES; PRIMARY CULTURES; RAT-LIVER; PHARMACOKINETICS; METABOLISM; GENDER;
Keywords:
ANESTHETICS, INTRAVENOUS, ALFENTANIL, FENTANYL, SUFENTANIL; ANALGESICS, OPIOID, ALFENTANIL, FENTANYL, SUFENTANIL; ENZYMES, CYTOCHROME P450 3A4; MENSTRUAL CYCLE, PHARMACOKINETICS, VARIABILITY, WOMEN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
E.D. Kharasch et al., "ASSESSMENT OF CYTOCHROME-P450 3A4 ACTIVITY DURING THE MENSTRUAL-CYCLEUSING ALFENTANIL AS A NONINVASIVE PROBE", Anesthesiology, 87(1), 1997, pp. 26-35

Abstract

Background: Gender-dependent differences in cytochrome P450 activity,drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform inthe human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. Methods: Alfentanil (20 mu g/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on threeseparate occasions during the same menstrual cycle: days 2 (menstrualphase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasmaalfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. Results: There was no significant difference inany measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. Conclusions: Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contributeto interindividual variability in alfentanil disposition In women. Ifother P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 00:30:18