Pharmacokinetics and disposition of [3h]dimethyl d/-curine dimethochloride in rats and mice

The concentration-time curve of [3H]dl-DCD following iv 350 yCi/kS in rats and 8.9 yCi/kg in mice were found to be a triexponential. In rats, the pharmacokinetic parameters calculated according t0 3-compart-ment open model were: 7r = 0.438,i'min, tl/2n =1.6 min. a = 0.013,i'min. t:/aa = 53.3 min. (3 = 0.00107,i'min. t1/2B = 1O.8 h, kLZ =0.230/min, kzi = O.197/min, k13 =0.014/min, k31 = 0.OO9/min, kio =0.006/min, ve = 0.306 l/kg. V2 =0.357 l/kg, V3 = 1.18 l/kg. Vd = 1.85 l/kg. clearance kio-ve = 1.96 ml/min/kg. D/AUC =1.98 ml/min/kg. Kinetic analysis indicated that [3H]dl-DCD WaS distributed rapidly into peripheral compartment from central compartment and eliminated at a slower rate. The highest levels of radioactivity were in liver and kidney. moderate in spleen. lung. muscle and heart. only trace of radioactivity was detected in brain and fat. After iv [3H]dl-DCD in pregnant mice, the radioactivity may cross the placental blrrier in SlIlall amounts into the fetus. After iv [3H]dl_DCD, the excretion of radioactivity in urine within 12 h was 65% of the dose while in bile was 20% in rats. In mice. the radioactivities excreted in urine and feces were 66% and 27%, respectively, of the dose in 72 h. The drug-plasma binding rate was found to be 13-21%. Paper radiochromatograms and ion-pair thin-layer chromatography of urine and, bile after iv [3H]dl-DCD revealed that the pattern of samples was remarkably similar to the pattern obtained from authentic [3H]dl-DCD.