Original Article

Assay of negative inotropism of bepridil on isolated guinea pig left atrial myocardium by simulating constant rate of absorption and elimination

Yuan Zhu, Ding-Ding Chen, Ling Su, De-Zai Dai


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.

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