Titre du document / Document title

Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors an update

Auteur(s) / Author(s)

SONG Jessica C. ^{(1 2)} ; WHITE C. Michael ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Drug Information Center, Hartford Hospital, Hartford, Connecticut, ETATS-UNIS
⁽²⁾ University of Connecticut School of Pharmacy, Storrs, Connecticut, ETATS-UNIS

Résumé / Abstract

The angiotensin converting enzyme (ACE) inhibitors are widely used in the management of essential hypertension, stable chronic heart failure, myocardial infarction (MI) and diabetic nephropathy. There is an increasing number of new agents to add to the nine ACE inhibitors (benazepril, cilazapril, delapril, fosinopril, lisinopril, pentopril, perindopril, quinapril and ramipril) reviewed in this journal in 1990. The pharmacokinetic properties of five newer ACE inhibitors (trandolapril, moexipril, spirapril, temocapril and imidapril) are reviewed in this update. All of these new agents are characterised by having a carboxyl functional groups and requiring hepatic activation to form pharmacologically active metabolites. They achieve peak plasma concentrations at similar times (t_max) to those of established agents. Three of these agents (trandolapril, moexipril and imidapril) require dosage reductions in patients with renal impairment. Dosage reductions of moexipril and temocapril are recommended for elderly patients, and dosages of moexipril should he lower in patients who are hepatically impaired. Moexipril should be taken 1 hour before meals, whereas other ACE inhibitors can be taken without regard to meals. The pharmacokinetics of warfarin are not altered by concomitant administration with trandolapril or moexipril. Although imidapril and spirapril have no effect on digoxin pharmacokinetics, the area under the concentration-time curve of imidapril and the peak plasma concentration of the active metabolite imidaprilat are decreased when imidapril is given together with digoxin. Although six ACE inhibitors (captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril) have been approved for use in heart failure by the US Food and Drug Administration, an overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27%. Captopril has been shown to have similar morbidity and mortality benefits to those of diuretics and β-blockers in hypertensive patients. Captopril has been shown to delay the progression of diabetic nephropathy, and enalapril and lisinopril prevent the development of nephropathy in normoalbuminuric patients with diabetes, ACE inhibitors are generally characterised by flat dose-response curves. Lisinopril is the only ACE inhibitor that exhibits a linear dose-response curve. Despite the fact that most ACE inhibitors are recommended for once-daily administration, only fosinopril, ramipril, and trandolapril have trough-to-peak effect ratios in excess of 50%.

Revue / Journal Title

Clinical pharmacokinetics   ISSN 0312-5963   CODEN CPKNDH 

Source / Source

2002, vol. 41, n^o3, pp. 207-224 (98 ref.)

Langue / Language

Anglais

Editeur / Publisher

Adis international, Auckland, NOUVELLE-ZELANDE  (1976) (Revue)

Mots-clés anglais / English Keywords

Digestive diseases ; Urinary system disease ; Enzyme ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Treatment ; Chemotherapy ; Review ; Hepatic disease ; Kidney disease ; Drug interaction ; Age ; Human ; Oral administration ; Pharmacokinetics ; Imidapril ; Spirapril ; Temocapril ; Moexipril ; Trandolapril ; Antihypertensive agent ; Peptidyl-dipeptidase A ; Enzyme inhibitor ; ACE inhibitor ;

Mots-clés français / French Keywords

Appareil digestif pathologie ; Appareil urinaire pathologie ; Enzyme ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Traitement ; Chimiothérapie ; Article synthèse ; Foie pathologie ; Rein pathologie ; Interaction médicamenteuse ; Age ; Homme ; Voie orale ; Pharmacocinétique ; Imidapril ; Spirapril ; Témocapril ; Moexipril ; Trandolapril ; Antihypertenseur ; Peptidyl-dipeptidase A ; Inhibiteur enzyme ; Inhibiteur angiotensin converting enzyme ;

Mots-clés espagnols / Spanish Keywords

Aparato digestivo patología ; Aparato urinario patología ; Enzima ; Hydrolases ; Peptidases ; Peptidyl-dipeptidases ; Tratamiento ; Quimioterapia ; Artículo síntesis ; Hígado patología ; Riñón patología ; Interacción medicamentosa ; Edad ; Hombre ; Vía oral ; Farmacocinética ; Imidapril ; Espirapril ; Temocapril ; Moexipril ; Trandolapril ; Antihipertensivo ; Peptidyl-dipeptidase A ; Inhibidor enzima ; Inhibidor angiotensin converting enzyme ;

Localisation / Location

INIST-CNRS, Cote INIST : 15599, 35400010061209.0050