Document Detail

Pharmacokinetic-pharmacodynamic modelling for captopril in healthy anaesthetized piglets.
MedLine Citation:
PMID:  8830975     Owner:  NLM     Status:  MEDLINE    
The use of the angiotensin converting enzyme inhibitor, captopril, specially in children, has been empirical. This is because the relationship between the pharmacokinetics and pharmacodynamics of captopril has not been clearly defined. It is not usually feasible to obtain the serial kinetic-dynamic data necessary to study this relationship in infants. The piglet was therefore investigated as an animal model in which to study the relationship between the kinetics and dynamics of captopril. The standard pharmacokinetic parameters for captopril in healthy anaesthetized piglets were found to be within the range reported for humans. ClTB was estimated to be 1.42 +/- 0.33 L h-1 kg(-1); t1/2 was 0.44 +/- 0.08 h; Vdss was calculated to be 0.64 +/- 0.13 L kg(-1); t1/2 and AUC0-infinity was estimated to be 145 +/- 27 ng h mL(-1). The observed haemodynamic response was qualitatively similar to that in humans. Aortic pressure was reduced by 42 +/- 18%; heart rate was reduced by 21 +/- 11%. A parametric pharmacokinetic (two-compartment)-pharmacodynamic (linear) model has been established to describe plasma captopril concentration and aortic pressure relationship. Based on the observed results, the piglet was considered to be a viable model for our purpose.
C M Pereira; Y K Tam; J Y Coe; P M Olley; R L Collins-Nakai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  17     ISSN:  0142-2782     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-12-10     Completed Date:  1996-12-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  365-72     Citation Subset:  IM    
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
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MeSH Terms
Angiotensin-Converting Enzyme Inhibitors / administration & dosage,  blood,  pharmacokinetics*,  pharmacology
Animals, Newborn
Blood Pressure / drug effects*
Captopril / administration & dosage,  blood,  pharmacokinetics*,  pharmacology
Chromatography, High Pressure Liquid
Heart Atria / drug effects
Heart Ventricles / drug effects
Myocardial Contraction / drug effects
Pulmonary Artery / metabolism
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 62571-86-2/Captopril

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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