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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Pharmacokinetics and pharmacodynamics of ramipril and piretanide administered alone and in combination
European Journal of Clinical Pharmacology, Volume 46, No. 6, Year 1994
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Description
The pharmacokinetics and pharmacodynamics of single oral doses of 5 mg ramipril and 6 mg piretanide administered separately and in combination were determined in a single blind, randomised, 3-period cross-over study in 24 healthy male volunteers. The peak plasma concentrations of ramipril and ramiprilat increased slightly (from 11.9 to 14.8 ng/ml, and from 6.39 to 8.96 ng/ml, respectively) as did the area under the plasma concentration-time curve of ramipril (0-4 h) and ramiprilat (0-24 h) (from 15.8 to 19.8 ng·ml-1·h, and from 63.4 to 74.6 ng·ml-1·h, respectively). The urinary excretion of ramiprilat also rose (from 6.82 to 7.73 % of dose) following simultaneous treatment with piretanide. These effects were probably due to reduced first-pass metabolism of ramipril/ramiprilat to inactive metabolites. The blood pressure lowering effect, the time course of inhibition of ACE activity in plasma and the concentration-response relationship for the inhibition of plasma ACE activity were not affected by piretanide. The peak plasma concentration of piretanide was somewhat reduced (from 285 to 244 ng/ml) following simultaneous treatment with ramipril. No other pharmacokinetic parameter was affected. Piretanide increased urine flow, and sodium, chloride and potassium excretion, especially during the first 2 hours following administration. These pharmacodynamic parameters were not affected by ramipril. Thus, simultaneous administration of single oral doses of ramipril and piretanide caused modest changes in the peak and average plasma concentrations of both drugs, which did not lead to detectable alterations in the pharmacodynamic parameters measured in healthy volunteers. © 1994 Springer-Verlag.
Authors & Co-Authors
Ruf, Guenther
Germany, Bad Krozingen
Universitäts Herzzentrum Freiburg Bad Krozingen
Gera, S.
France, Gentilly
Sanofi S.a.
Luus, Hermanus Gerhardus
South Africa, Bloemfontein
University of the Free State
Trenk, Dietmar
Germany, Bad Krozingen
Universitäts Herzzentrum Freiburg Bad Krozingen
de la Rey, N.
South Africa, Bloemfontein
University of the Free State
Löffler, Kurt
France, Gentilly
Sanofi S.a.
Schulz, Wolfgang
France, Gentilly
Sanofi S.a.
Jähnchen, Eberhard
Germany, Bad Krozingen
Universitäts Herzzentrum Freiburg Bad Krozingen
Statistics
Citations: 10
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1007/BF00196113
e-ISSN:
14321041
Research Areas
Disability
Health System And Policy
Noncommunicable Diseases
Participants Gender
Male