[Assay of negative inotropism of bepridil on isolated guinea pig left atrial myocardium by simulating constant rate of absorption and elimination].
The pharmacodynamic characteristic of negative inotropic effect of bepridil on isolated guinea pig cardiac atrium was conducted by gradient perfusion with constant rate of bepridil ranging from 0-20 mumol.L-1 and inverse, simulating a fixed pharmacokinetic parameters of K(a) and K(e), respectively. A counter-clockwise hysteresis loop of negative inotropism of bepridil was presented. Fixing Cp, T, and E by pharmacokinetics/pharmacodynamics (PK/PD) non-parameter model, the hysteresis loop was collapsed in figure plotting C(e) against E. The estimated K(eo) = 0.03 +/- 0.023 h-1, an apparent T1/2 of pharmacological effect was measured, and about 80-fold as long as the pharmacokinetic T1/2. It was suggested that the long-lasting effect of bepridil was partly due to the slow elimination rate from the effect compartment.
Zhu
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Y
Research Division of Pharmacology, China Pharmaceutical University, Nanjing.
Chen
D D
DD
Su
L
L
Dai
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DZ
D000042:Absorption; D000818:Animals; D015764:Bepridil / Q000493:pharmacokinetics / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*
D015764:Bepridil