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PHARMACOKINETIC–PHARMACODYNAMIC MODELLING FOR CAPTOPRIL IN HEALTHY ANAESTHETIZED PIGLETS

✍ Scribed by Conrad M. Pereira; Yun K. Tam; James Y. Coe; Peter M. Olley; Ruth L. Collins-Nakai


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
441 KB
Volume
17
Category
Article
ISSN
0142-2782

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✦ Synopsis


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. ClTe was estimated to be 1.423~ 0.33Lh-I kg-I; t1/2 was 044*0*08h; vd, was calculated to be 0.642Z0.13 Lkg-'; t l l 2 and A U G , was estimated to be 145*27nghmL-'. The observed haemodynamic response was qualitatively similar to that in humans. Aortic pressure was reduced by 422~18%; heart rate was reduced by 21 *ll%. A parametric pharmacokinetic (twocompartment)-phannacodynamic (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.


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