Diltiazem concentrations in plasma vs PR intervals on electrocardiogram in 8 men.
OBJECTIVE
To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men.


METHODS
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.


CONCLUSIONS
Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model.
Liu
X D
XD
Centre of Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Xie
L
L
Zhong
B
B
Xu
Q
Q
Luan
L B
LB
Liu
G Q
GQ
D000328:Adult; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology; D004110:Diltiazem / Q000493:pharmacokinetics* / Q000494:pharmacology; D004361:Drug Tolerance; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008297:Male
D002121:Calcium Channel Blockers; D004110:Diltiazem