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Titolo:
The effect of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of warfarin in humans
Autore:
Niopas, I; Toon, S; Aarons, L; Rowland, M;
Indirizzi:
Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England Univ Manchester Manchester Lancs England M13 9PL M13 9PL, Lancs, England Aristotelian Univ Salonika, Dept Pharm, GR-54006 Salonika, Greece Aristotelian Univ Salonika Salonika Greece GR-54006 006 Salonika, Greece Medeval Ltd, Manchester M15 4SH, Lancs, England Medeval Ltd Manchester Lancs England M15 4SH ster M15 4SH, Lancs, England
Titolo Testata:
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 5, volume: 55, anno: 1999,
pagine: 399 - 404
SICI:
0031-6970(199907)55:5<399:TEOCOT>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
DRUG-INTERACTIONS; STEREOSELECTIVE INTERACTION; ANTICOAGULATED PATIENTS; RACEMIC WARFARIN; ENANTIOMERS; METABOLISM; RANITIDINE; INHIBITION;
Keywords:
warfarin; cimetidine; drug-drug interaction;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Rowland, M Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England Univ Manchester Manchester Lancs England M13 9PL ancs, England
Citazione:
I. Niopas et al., "The effect of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of warfarin in humans", EUR J CL PH, 55(5), 1999, pp. 399-404

Abstract

Objective: The interaction of multiple oral doses of cimetidine on the steady-state pharmacokinetics and pharmacodynamics of warfarin was investigated in six healthy male volunteers. Methods: The subjects were given individually adjusted doses of warfarin to achieve therapeutic levels of prothrombin activity. The established dailymaintenance oral dose of warfarin was kept stable throughout the trial and, on study days 8-14, each volunteer received a 800-mg daily dose of cimetidine. The degree of anticoagulant response produced by warfarin was quantified by the determination of both the prothrombin time and factor-VII clotting activity. Results: Cimetidine co-administration had no significant effect on the pharmacokinetics of the more potent S-warfarin but significantly increased by 28% (P < 0.05) mean R-warfarin trough plasma concentrations and decreased by 23% (P < 0.05) mean R-warfarin apparent clearance. Both prothrombin time and factor-VII clotting activity displayed considerable inter-subject variability and were not significantly affected by concurrent cimetidine treatment. The reduction of apparent clearance of li-warfarin by cimetidine was found to be the effect of inhibition of the formation of warfarin metabolitesas determined by apparent formation clearance values (+/- SD) of R-6-hydroxywarfarin (31.1 +/- 7.4 ml/h baseline; 18.5 +/- 4.5 ml/h at end of cimetidine treatment; P < 0.01), and R-7-hydroxywarfarin (6.9 +/- 1.3 ml/h baseline; 4.3 +/- 1.1 ml/h at end of cimetidine treatment; P < 0.01). Conclusion: Cimetidine stereoselectively affects the steady-state pharmacokinetics of warfarin by inhibiting the disposition of the less potent R-warfarin in humans. However, this interaction is likely to be of minimal clinical significance in most patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 16:16:06