Yoshikawa M, Endo H, Otsuka M, Yamaguchi I, Harigaya S
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Drug Metab Dispos. 1988 Sep-Oct;16(5):754-8.
The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs. The maximum concentrations of free DA in plasma after oral administration of TA-870 were 150 ng/ml in the rat (30 mg/kg) and 234 ng/ml in the dog (33.5 mg/kg). On the contrary, the maximum plasma concentrations after oral administration of DA at an equimolar dose to TA-870 were 12 ng/ml in the rat (12 mg/kg) and 36 ng/ml in the dog (13.5 mg/kg). The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species. The peak tissue levels of radioactivity in rats after oral administration of [14C]TA-870 (30 mg/kg) were also 5.5 times higher in the liver and 1-2 times higher in other tissues than those after [14C]DA dose (12 mg/kg). In rats, the main excretion route of radioactivity after oral administration of [14C]TA-870 or DA was via the urine. The total recoveries of radioactivity in the urine and feces were 91-96% of the dose within 24 hr for both compounds. Biliary excretion in rats accounted for 19.8% of the dose of [14C]TA-870 and 12.6% of the dose of [14C]DA within 24 hr. These results demonstrate that TA-870 was well absorbed from the digestive tract, extensively metabolized to dopamine, and proved to be an orally usable dopamine prodrug.
在大鼠和狗中比较了多巴胺衍生物TA - 870和多巴胺（DA）口服给药后的药代动力学。口服TA - 870后，大鼠（30mg/kg）血浆中游离DA的最大浓度为150ng/ml，狗（33.5mg/kg）为234ng/ml。相反，以与TA - 870等摩尔剂量口服DA后，大鼠（12mg/kg）血浆最大浓度为12ng/ml，狗（13.5mg/kg）为36ng/ml。在两种动物中，口服TA - 870（30或33.5mg/kg）后血浆中游离DA的AUC值比口服DA后高4 - 6倍。口服[¹⁴C]TA - 870（30mg/kg）后，大鼠肝脏中放射性的峰值组织水平也比口服[¹⁴C]DA剂量（12mg/kg）后高5.5倍，其他组织中高1 - 2倍。在大鼠中，口服[¹⁴C]TA - 870或DA后放射性的主要排泄途径是通过尿液。两种化合物在24小时内尿液和粪便中放射性的总回收率为给药剂量的91 - 96%。大鼠胆汁排泄在24小时内占[¹⁴C]TA - 870剂量的19.8%，占[¹⁴C]DA剂量的12.6%。这些结果表明，TA - 870从消化道吸收良好，广泛代谢为多巴胺，并被证明是一种可口服的多巴胺前药。
