title: Kinetics, safety, and efficacy of ramipril after long-term administration in hemodialyzed patients.
abstract: We studied the efficacy and safety of ramipril and the kinetics of its active moiety ramiprilat in 12 hypertensive patients receiving regular hemodialysis, after a single dose and after long-term (28 days) administration. Patients received 2.5 mg ramipril after each hemodialysis. On days 1 and 29, ramipril was administered 4 h before the hemodialysis and serial blood samples were obtained for 9 h for determination of pharmacokinetic parameters. Tolerability was good, and all patients completed the study. There was a high degree of angiotensin-converting enzyme (ACE) inhibition throughout the study. Ramipril had a clear-cut antihypertensive effect. Long-term administration of ramipril did not modify the time to peak ramiprilat concentration, but increased the mean maximal concentration significantly: 20.2 +/- 12.7 vs. 10.4 +/- 7.1 ng center dot ml-1. The mean accumulation ratio was 2.2. Ramiprilat hemodialysis clearance was 31.7 ml/min (range 4.2-64.9 ml/min) on day 1 and 21.0 ml/min (range 7.9-56.5 ml/min) on day 29. Ramipril 2.5 mg, administered after hemodialysis, appears to be safe and effective in hypertensive patients receiving periodic hemodialysis. Despite an increase in ramiprilat concentration from day 1 to day 29, the steady state was reached. We describe the role of nonrenal clearance of ramiprilat.
authors.affiliation: Department of Nephrology, C.H.U. Rouen, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Fillastre
authors.forename: J C
authors.initials: JC
authors.lastname: Baguet
authors.forename: D
authors.initials: D
authors.lastname: Dubois
authors.forename: J
authors.initials: J
authors.lastname: Vauquier
authors.forename: M
authors.initials: M
authors.lastname: Godin
authors.forename: B
authors.initials: B
authors.lastname: Legallicier
authors.forename: H G
authors.initials: HG
authors.lastname: Luus
authors.forename: N
authors.initials: N
authors.lastname: de la Rey
authors.forename: N
authors.initials: N
authors.lastname: Carcone
authors.forename: R
authors.initials: R
authors.lastname: Genthon
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011355:Prodrugs; D017257:Ramipril / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D006435:Renal Dialysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011355:Prodrugs; C052549:ramiprilat; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril