Fu K K, DeGregorio M W, Phillips J W
Department of Radiation Oncology, University of California, San Francisco 94143.
NCI Monogr. 1988(6):123-7.
Our purpose of this study was to determine whether whole-body, continuous low-dose-rate irradiation (CLDRI) alters the plasma and/or tumor platinum pharmacokinetics after ip bolus injection or ip infusion as a possible mechanism of interaction between CLDRI and cisplatin. The C3Hf/Sed mice bearing SCCVII/SF tumors were given 6 mg cisplatin/kg ip by bolus injection or an ip infusion of 0.25 mg cisplatin.kg-1.hour-1 for 48 hours with and without CLDRI at 0.56 Gy/hr for 24 or 48 hours. Plasma and tumor platinum concentrations were determined with an atomic absorption spectrophotometer at appropriate intervals during infusion and up to 48 hours after drug administration. Both total and ultrafilterable plasma platinum followed a biphasic elimination after ip bolus injection, whereas only a prolonged single-phase elimination was seen after ip infusion. Tumor uptake of platinum appeared to follow a passive diffusion pattern with a prolonged cellular retention of platinum. Whole-body CLDRI had no apparent effect on the pharmacokinetics of plasma and tumor platinum administered by ip bolus injection or prolonged continuous infusion.
本研究的目的是确定全身连续低剂量率照射（CLDRI）在腹腔推注或腹腔输注顺铂后是否会改变血浆和/或肿瘤铂的药代动力学，这可能是CLDRI与顺铂之间相互作用的一种机制。给携带SCCVII/SF肿瘤的C3Hf/Sed小鼠腹腔推注6 mg顺铂/kg，或腹腔输注0.25 mg顺铂·kg⁻¹·小时⁻¹，持续48小时，同时在0.56 Gy/小时的剂量下进行或不进行24或48小时的CLDRI。在输注期间及给药后长达48小时的适当时间间隔，用原子吸收分光光度计测定血浆和肿瘤铂浓度。腹腔推注后，血浆总铂和可超滤铂均呈现双相消除，而腹腔输注后仅出现延长的单相消除。铂在肿瘤中的摄取似乎遵循被动扩散模式，铂在细胞内的保留时间延长。全身CLDRI对腹腔推注或长时间持续输注给药的血浆和肿瘤铂的药代动力学没有明显影响。
