Pharmacokinetic-pharmacodynamic analysis of changrolin in dogs with arrhythmia.

The pharmacokinetics and pharmacodynamics of changrolin (CRL) were studied in 7 dogs with arrhythmia induced by coronary artery ligature. The ECG and the percentage of reduction ratio of ventricular premature were used to evaluate the effect of CRL, and an HPLC method was used to determine the serum drug concentration. A pharmacokinetic program was used to fit concentration-time (C-T) data and a combined pharmacokinetic-pharmacodynamic model was used to analyze effect-time (E-T) data in individual dogs. After infusion with CRL 83.33 micrograms.kg-1.min-1 for 60 min, it was found that K10, T1/2, Vd, Cl and Ce were 0.0087 min-1, 78.03 min, 40.55 ml.kg-1, 0.42 ml.kg-1.min-1, and 2.01 micrograms.ml-1, respectively.