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Titolo:
Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam
Autore:
Yuan, R; Flockhart, DA; Balian, JD;
Indirizzi:
US FDA, CDER, OPS, OCPB,DPE 1, Rockville, MD 20857 USA US FDA Rockville MD USA 20857 R, OPS, OCPB,DPE 1, Rockville, MD 20857 USA Georgetown Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA Georgetown Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 armacol, Washington, DC 20007 USA
Titolo Testata:
JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 11, volume: 39, anno: 1999,
pagine: 1109 - 1125
SICI:
0091-2700(199911)39:11<1109:PAPCOM>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; SYSTEMIC ANTIMYCOTICS KETOCONAZOLE; ORAL DOSE PHARMACOKINETICS; HEALTHY-VOLUNTEERS; IN-VITRO; CLINICAL PHARMACOKINETICS; PLASMA-CONCENTRATIONS; DYNAMIC CONSEQUENCES; CYTOCHROME-P450 3A; HUMAN-PERFORMANCE;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
92
Recensione:
Indirizzi per estratti:
Indirizzo: Yuan, R US FDA, CDER, OPS, OCPB,DPE 1, HFD-860,5600 Fishers Lane,Woodmont 2 Bldg,Room 40, Rockville, MD 20857 USA US FDA HFD-860,5600 Fishers Lane,Woodmont 2 Bldg,Room 40 Rockville MD USA 20857
Citazione:
R. Yuan et al., "Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam", J CLIN PHAR, 39(11), 1999, pp. 1109-1125

Abstract

This review was conducted to identify the current data on drug interactions with alprazolam, midazolam, and triazolam to guide practitioners in the use of these drugs. The Medline electronic database from 1966 through 1998 was used to identify clinical studies of the pharmacokinetic effect of drugson these three benzodiazepines. Of a total of 491 literature reports identified, 59 prospective studies met our selection criteria. The pharmacokinetic parameters of AUC, C-max, t(1/2), and t(max) were evaluated for changes following an interaction. To allow comparison between studies, changes in the parameters were normalized relative to the control values. Pharmacodynamic effects and measures, when reported in the original studies as statistically significant, were classified as a strong interaction, and when the interaction was present but not statistically significant, they were classified as mild in this review. As a result, clinically significant drug interactions were noted for all three benzodiazepines, although it is clear that statistically significant pharmacokinetic changes do not always translate into clinically significant pharmacodynamic consequences. All three benzodiazepines were susceptible to drug interactions, but oral dosing of midazolam and triazolam resulted in greater alterations in the pharamcokinetic parameters than alprazolam due to their larger presystemic extraction. Ketoconazole and itraconazole were found to be the most potent metabolic inhibitors that prolonged the duration of or intensified the magnitude of the dynamic response produced by the three benzodiazepines. Rifampin, carbamazepine, and phenytoin were noted to be potent metabolic inducers, and their treatments result in loss of benzodiazepine therapeutic efficacy In conclusion, potentmetabolic inhibitors and inducers can either significantly prolong or diminish the dynamic effects of benzodiazepines via their influence on the pharmacokinetics of benzodiazepines. (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 16:04:45