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Titolo:
PHARMACOKINETIC-PHARMACODYNAMIC MODEL RELATING ZABICIPRILAT PLASMA-CONCENTRATIONS TO BRACHIAL AND FEMORAL HEMODYNAMIC-EFFECTS IN NORMOTENSIVE VOLUNTEERS
Autore:
BELLISSANT E; GIUDICELLI JF;
Indirizzi:
CTR HOSP BICETRE,SERV PHARMACOL CLIN,78 RUE GEN LECLERC F-94275 LE KREMLIN BICETR FRANCE CTR HOSP BICETRE,SERV PHARMACOL CLIN F-94275 LE KREMLIN BICETR FRANCE FAC MED,LAB PHARMACOL CLIN RENNES FRANCE
Titolo Testata:
British journal of clinical pharmacology
fascicolo: 4, volume: 46, anno: 1998,
pagine: 383 - 393
SICI:
0306-5251(1998)46:4<383:PMRZP>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANGIOTENSIN-CONVERTING-ENZYME; HEALTHY-VOLUNTEERS; DRUG DEVELOPMENT; INHIBITOR;
Keywords:
ZABICIPRIL; HEALTHY VOLUNTEERS; HEMODYNAMICS; PK-PD MODELING; CONCENTRATION-EFFECT RELATIONSHIP; SIGMOID MODEL; EFFECT COMPARTMENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
23
Recensione:
Indirizzi per estratti:
Citazione:
E. Bellissant e J.F. Giudicelli, "PHARMACOKINETIC-PHARMACODYNAMIC MODEL RELATING ZABICIPRILAT PLASMA-CONCENTRATIONS TO BRACHIAL AND FEMORAL HEMODYNAMIC-EFFECTS IN NORMOTENSIVE VOLUNTEERS", British journal of clinical pharmacology, 46(4), 1998, pp. 383-393

Abstract

Aims To investigate, in healthy volunteers, the relationship between the plasma concentrations (C, ng ml(-1)) of zabiciprilat, the active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) zabicipril, and the effects (E) induced on plasma converting enzyme activity (PCEA, nmol ml(-1) min(-1)), brachial and femoral artery flows (BAF, FAF, ml min(-1)) and brachial and femoral vascular resistances (BVR,FVR, mmHg.s ml(-1)) after a single oral administration of two doses (0.5 and 2.5 mg) of zabicipril. Methods The study was placebo-controlled, randomized, double-blind and crossover. E was related to C by the Hill model, E = E-max.C-Y/(CE50Y + C-Y), fitted to the data of both doses simultaneously. Results We obtained (mean +/- s.d. ) E-max = -99 +/-1%, CE50 = 2.2 +/- 1.0 ng ml(-1) and gamma = 1.0 +/- 0.4 for PCEA, E-max=55+/-26 ml min(-1), CE50=5.1 +/- 4.0 ng ml(-1) and gamma=2.4+/-1.6for BAF, and E-max= -45+/-10%, CE50=2.0+/-1.3 ng ml(-1) and gamma = 2.3 +/- 1.4 for BVR. The parameters obtained for FAF and FVR were similar to those obtained for BAF and BVR, respectively. The CE95 (C required to induce 95% of E-max) varies from 7 to 17 ng ml(-1) for haemodynamic effects. Conclusions As zabiciprilat peak plasma concentrations average 20 ng ml(-1) after the 2.5 mg dose of zabicipril, this dose of the drug should be sufficient to induce optimal haemodynamic effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 12:32:17