Tinker N, De Spiegeleer B, Sharma H, Jackson H, McAuliffe C, Reman J P
Department of Chemistry, UMIST, Manchester, U.K.
Int J Rad Appl Instrum B. 1990;17(4):427-36. doi: 10.1016/0883-2897(90)90112-e.
[195mPt]carboplatin has been administered intravenously, intraperitoneally and orally to Wistar rats and the tissue distribution, metabolism, and pharmacokinetics of the drug investigated. The urinary and faecal excretion and toxicity following oral [195mPt]carboplatin administration has also been studied. Virtually identical results have been observed following i.v. and i.p. administration, indicating a rapid absorption of the unaltered compound from the abdominal cavity into the systemic circulation. Thus i.p. administered drug should produce a similar therapeutic response as i.v. administration, but may produce an additional local effect within the peritoneal cavity. Orally administered compound shows a pattern of distribution which is similar to that following parenteral injection for all tissues (except for the increased relative concentration in the stomach tissue), the concentration being lower by a factor of 4-5. However, the overall fraction of the dose retained within the body at 24 h is similar to that following i.v. administration. The toxicity is considerably lower for the orally administered drug compared with i.v. injection. These results clearly show that oral doses could be adjusted to produce a comparable therapeutic effect as i.v. or i.p. doses, and should also result in a higher efficacy against gastric carcinomas than achievable with parenteral administration.
已对Wistar大鼠静脉内、腹腔内和口服给予[195mPt]卡铂，并研究了该药物的组织分布、代谢和药代动力学。还研究了口服[195mPt]卡铂后的尿液和粪便排泄及毒性。静脉内和腹腔内给药后观察到几乎相同的结果，表明未改变的化合物从腹腔迅速吸收进入体循环。因此，腹腔内给药的药物应产生与静脉内给药相似的治疗反应，但可能在腹腔内产生额外的局部作用。口服化合物的分布模式与所有组织经胃肠外注射后的分布模式相似（胃组织中相对浓度增加除外），浓度低4-5倍。然而，24小时内体内保留的总剂量分数与静脉内给药后的相似。与静脉内注射相比，口服药物的毒性要低得多。这些结果清楚地表明，口服剂量可以调整以产生与静脉内或腹腔内剂量相当的治疗效果，并且与胃肠外给药相比，对胃癌的疗效也应该更高。
