Elferink F, van der Vijgh W J, Klein I, ten Bokkel Huinink W W, Dubbelman R, McVie J G
Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
Cancer Chemother Pharmacol. 1988;21(1):57-60. doi: 10.1007/BF00262740.
The pharmacokinetics of carboplatin, ultrafilterable platinum, and total platinum after intraperitoneal (i.p.) administration were studied in peritoneal fluid, plasma, red blood cells (RBCs), and urine during a phase-I trial in patients with minimal, residual ovarian cancer. Samples were collected from 7 patients who had received carboplatin (200-500 mg/m2) in 21 dialysis fluid. The fluid was withdrawn after a 4-h dwell. Platinum concentrations were measured by flameless atomic absorption spectrometry, and intact carboplatin was determined by HPLC with electrochemical detection. Peak concentrations of carboplatin in plasma were obtained 2 h after the end of instillation. The mean ratio of peak concentrations of carboplatin in instilled fluid and plasma was 24 +/- 11. The peritoneal clearance of carboplatin was 8 +/- 3 ml/min, which was 12 times less than the plasma clearance (93 +/- 32 ml/min). Due to this clearance ratio, the AUCs for the peritoneal cavity were about 10 times higher than those for plasma. On average, 34% +/- 14% of the dose was still present in the instillation fluid that had been withdrawn after a dwell time of 4 h. In plasma, the mean value of AUC/Dnet (Dnet = Dose - amount recovered from the peritoneal cavity) after i.p. administration was comparable with that of AUC/D after i.v. administration. This means that unrecovered carboplatin (66%) was completely absorbed from the peritoneal cavity. It may be expected from this bioavailability that the maximum tolerated dose (MTD) of i.p.-administered carboplatin with a 4-h dwell is around 1.5 times higher than that after i.v. administration. Overall pharmacokinetic parameters of carboplatin and platinum in plasma were comparable after i.p. and i.v. administration.
在一项针对微小残留卵巢癌患者的I期试验中，研究了腹腔内（i.p.）给药后卡铂、可超滤铂和总铂在腹腔液、血浆、红细胞（RBC）和尿液中的药代动力学。从7名接受卡铂（200 - 500 mg/m²）的患者收集样本，药物溶解于21份透析液中。4小时保留后抽出液体。通过无火焰原子吸收光谱法测量铂浓度，通过带有电化学检测的高效液相色谱法测定完整的卡铂。滴注结束后2小时获得血浆中卡铂的峰值浓度。滴注液和血浆中卡铂峰值浓度的平均比值为24±11。卡铂的腹腔清除率为8±3 ml/min，比血浆清除率（93±32 ml/min）低12倍。由于这种清除率比值，腹腔的AUC约比血浆高10倍。平均而言，在4小时保留时间后抽出的滴注液中仍有34%±14%的剂量。在血浆中，腹腔给药后AUC/Dnet（Dnet = 剂量 - 从腹腔回收的量）的平均值与静脉给药后AUC/D的平均值相当。这意味着未回收的卡铂（66%）从腹腔中被完全吸收。从这种生物利用度可以预期，腹腔内给药且保留4小时的卡铂最大耐受剂量（MTD）比静脉给药后高约1.5倍。腹腔和静脉给药后血浆中卡铂和铂的总体药代动力学参数相当。
