Segal J L, Cunningham R F, Dayton P G, Israili Z H
Drug Metab Dispos. 1976 Mar-Apr;4(2):140-6.
Studies with [14C]methylphenidate-HCl were carried out in rats administered the drug intravenously or intraperitoneally. Levels of total radioactivity and parent drug were measured in plasma, brain, and certain brain regions up to 6 hr after dosing. The intravenous route of administration was characterized by rapid entry into brain; during the first half hour, brain levels were 3- to 6-fold higher than those obtained by the intraperitoneal route. At later time periods, brain and plasma concentration for both routes were comparable, and the decline of drug concentrations in brain paralleled that in plasma. No significant variance was found in regional distribution of drug in brain. Whereas the major fraction of circulating drug consisted of metabolites, predominantly unchanged drug was found in brain. After intravenous injection of [14C]ritalinic acid (the major metabolite of methylphenidate), no substantial concentrations were found in brain.
用[14C]盐酸哌醋甲酯对大鼠进行了静脉或腹腔注射给药的研究。给药后长达6小时，测量了血浆、脑及某些脑区的总放射性水平和母体药物水平。静脉给药途径的特点是药物迅速进入脑内；在前半小时内，脑内水平比腹腔给药途径高3至6倍。在随后的时间段，两种给药途径的脑和血浆浓度相当，脑内药物浓度的下降与血浆中的下降情况平行。未发现药物在脑内的区域分布有显著差异。虽然循环药物的主要部分由代谢物组成，但脑内主要发现的是未变化的药物。静脉注射[14C]利他林酸（哌醋甲酯的主要代谢物）后，脑内未发现大量浓度。
