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Titolo:
Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients
Autore:
Bellissant, E; Giudicelli, JF;
Indirizzi:
Hop Bicetre, Serv Pharmacol Clin, Le Kremlin Bicetre, France Hop Bicetre Le Kremlin Bicetre France Clin, Le Kremlin Bicetre, France Fac Med, Lab Pharmacol Clin, Rennes, France Fac Med Rennes FranceFac Med, Lab Pharmacol Clin, Rennes, France
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 1, volume: 52, anno: 2001,
pagine: 25 - 33
SICI:
0306-5251(200107)52:1<25:PMFPRH>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANGIOTENSIN-CONVERTING ENZYME; PLASMA-CONCENTRATIONS; DRUG DEVELOPMENT; INHIBITION; HEMODYNAMICS; RENIN;
Keywords:
concentration-effect relationship; congestive heart failure patients; effect compartment; haemodynamics; healthy volunteers; perindopril; PK-PD modelling; sigmoid model;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Giudicelli, JF Ctr Hosp Bicetre, Serv Pharmacol Clin, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France Ctr Hosp Bicetre 78 Rue Gen Leclerc Le Kremlin Bicetre France F-94275
Citazione:
E. Bellissant e J.F. Giudicelli, "Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients", BR J CL PH, 52(1), 2001, pp. 25-33

Abstract

Aims We compared the relationships between the plasma concentrations (C) of perindoprilat, active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) perindopril, and the effects (E) induced on plasma converting enzyme activity (PCEA) and brachial vascular resistance (BVR) in healthyvolunteers (HV) and in congestive heart failure (CHF) patients after single oral doses of perindopril. Methods Six HV received three doses of perindopril (4, 8, 16 mg) in a placebo-controlled, randomized, double-blind, crossover study whereas 10 CHF patients received one dose (4 mg) in an open study. Each variable was determined before and 6-12 times after drug intake. E (% variations from baseline)were individually related to C (ng ml(-1)) by the Hill model E=E-max.C-gamma/( CE50gamma + C-gamma). When data showed a hysteresis loop, an effect compartment was used. Results (means +/-s.d. ) In HV, relationships between C and E were direct whereas in CHF patients, they showed hysteresis loops with optimal k(e0) values of 0.13 +/- 0.16 and 0.13 +/- 0.07 h(-1) for PCEA and BVR, respectively. For PCEA, with E-max set to -100%, CE50 = 1.87 +/- 0.60 and 1.36 +/- 1.33ng ml(-1) (P = 0.34) and gamma = 0.90 +/- 0.13 and 1.11 +/- 0.47 (P = 0.23) in HV and CHF patients, respectively. For BVR, E-max=-41 +/- 14% and -60 /- 7% (P = 0.02), CE50 = 4.95 +/- 2.62 and 1.38 +/- 0.85 ng ml(-1) (P = 0.02), and gamma = 2.25 +/- 1.54 and 3.06 +/- 1.37 (P = 0.32) in HV and CHF patients, respectively. Conclusions Whereas concentration-effect relationships were similar in HV and CHF patients for PCEA blockade, they strongly differed for regional haemodynamics. This result probably expresses the different involvements, in HV and CHF patients, of angiotensinergic and nonangiotensinergic mechanisms in the haemodynamic effects of ACEIs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/10/20 alle ore 16:42:02