Pharmacokinetic-pharmacodynamic modelling for captopril in healthy anaesthetized piglets.
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.
Pereira
C M
CM
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Tam
Y K
YK
Coe
J Y
JY
Olley
P M
PM
Collins-Nakai
R L
RL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011651:Pulmonary Artery / Q000378:metabolism; D012984:Software; D013552:Swine
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril