Fujiwara K, Yamauchi H, Sawada S, Koike H, Mohri H, Ohishi Y, Kohno I
Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Japan.
Gan To Kagaku Ryoho. 1992 Dec;19(14):2373-9.
The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.
将腹腔内注射（IP）环磷酰胺铂（CBDCA）的药代动力学与静脉注射（IV）CBDCA进行了比较，并对晚期卵巢癌患者进行了静脉注射顺铂（CPM）联合400mg/m² IP CBDCA的剂量递增研究。腹腔内注射CBDCA后血清中游离铂（F-Pt）的最大浓度约为静脉注射CBDCA后F-Pt浓度的1/3。腹腔内注射CBDCA后，血清中的F-Pt在给药后12小时内仍占总铂的90%以上。腹腔内注射CBDCA后血清中F-Pt的半衰期（t1/2）比静脉注射CBDCA后的t1/2长两倍，表明CBDCA的腹腔清除缓慢。腹腔内注射CBDCA后的曲线下面积（AUC）约为静脉注射CBDCA后AUC的67%。腹腔内注射CBDCA后铂的累积尿排泄量（CUS）为静脉注射后CUS的37%。静脉注射CPM联合400mg/m² IP CBDCA的最大耐受剂量为550-600mg/m²。这种联合治疗的剂量限制因素是白细胞减少。本研究中血小板减少较轻。400mg/m² IP CBDCA和550-600mg/m²的联合似乎对大多数晚期卵巢癌患者是一种可耐受且可重复的治疗方法。由于血小板减少较轻，且药代动力学显示腹腔内注射CBDCA后血清中游离铂的AUC较小，因此应考虑对IP CBDCA进行剂量递增研究。
