Original Articles

Disposition of [3H] dimethyl-l-curine dimetho-chloride in rats

Authors: Xi-can Tang, Yu-e Wang, Jie Feng, Yu-long Zhang, Dao-ling Zhuang

Abstract

The distribution, excretion and metabolism of [3H] dimethyl-l-curine dimethochloride (DCD) and its pharmacokinetics in rats were studied. After an iv bolus of [3H]DCD 75μCi/kg (375μg/kg), the disappearance of DCD from blood fits best to a triexponential model. The pharmacokinetic parameters calculated according to three-compartment open model were: π= 0.517/min, t1/2π= 1.3 min , α= 0.0111/min,t1/2α= 62.4 min, β=0.00116 /min, t1/2β=10 h, k12=0.319/min, k21=0.179/min, k13=0.012/min, k31=0.002/min, k10 =0.018/min, v1=43 ml (0.22 l/kg). v2=77ml (0.39 l/kg),v3= 617ml (3.1 l/kg), vd=737 ml (3.7 l/kg) clearance k10∙v1=0.76 ml/min, D/AUC =0.76 ml/min. These results imply that [3H]DCD distributed widely, passed quickly into peripheral compartments and was eliminated at a slower rate.
Radioactivity levels were highest in kidney and moderate in liver, lung and skelatal muscle. Only traces of radioactivity were detected in fat and brain.
After an iv bolus of [3H]DCD, 48-72% of the radioactivity was excreted in urine and 6.3% in feces in 24 h. About 13% of the iv radioactivity was recovered from bile in 12 h.
paper radiochromatograms of urine and bile after iv [3H]DCD revealed a pattern remarkably similar to the pattern obtained from the scanning of the authentic [3H]DCD. By ion-pair thin-layer chromatography, no metabolite of DCD was found in urine and bile.
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