ABSTRACT
AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model.
Subject(s)
Calcium Channel Blockers/pharmacokinetics , Diltiazem/pharmacokinetics , Electrocardiography/drug effects , Adult , Calcium Channel Blockers/pharmacology , Diltiazem/pharmacology , Drug Tolerance , Humans , MaleABSTRACT
For increasing the choleretic action of armillarision-A, a new formulation of rapid-dissolution tablet (A) was developed. The effect of A, a marketed amillarisin-A tablet (B) and a armillarisin-A Na sterile power (C) on rats biliation in vivo were investigated. The dissolution rates of A and B were also determined. The results demonstrate that the choleretic action of A is equal to C but superior to B, and the dissolution rate of A is higher than B. Moreover, the armillarisin-A dissolved percentage of A in vitro at time t was well correlated with the biliation net accumulative amount in vivo at time 3t.
