TY - JOUR AU - Zhu Yuan AU - Chen Ding-Ding AU - Su Ling AU - Dai De-Zai PY - 2016 TI - Assay of negative inotropism of bepridil on isolated guinea pig left atrial myocardium by simulating constant rate of absorption and elimination JF - Acta Pharmacologica Sinica; Vol 14, No 2 (March 1993): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/8731