PHARMACOKINETICS OF FREE AND TOTAL PLATINUM SPECIES AFTER RAPID AND PROLONGED INFUSIONS OF CISPLATIN
PHARMACOKINETICS OF FREE AND TOTAL PLATINUM SPECIES AFTER RAPID AND PROLONGED INFUSIONS OF CISPLATIN
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DOI：
10.1038/clpt.1986.24
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发表时间：
1986-02-01
影响因子：
6.7
通讯作者：
PINEDO, HM
中科院分区：
文献类型：
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作者：
VERMORKEN, JB;VANDERVIJGH, WJF;PINEDO, HM
对 51 名接受顺铂输注的患者进行了药代动力学研究。使用两种治疗方案（一天或每天，持续 5 天）和三种输注方案（4 至 15 分钟、2 至 3 小时或 24 小时）。顺铂的日剂量为20至120 mg/m2。截至第 5 天的总铂动力学研究显示，仅在输注后的初始阶段存在差异。峰值水平与剂量和时间表相关，衰减曲线中的初始 t12 值仅与时间表相关（平均值：快速输注为 13 分钟，2 至 3 小时输注为 40.3 分钟，24 小时输注为 220.5 分钟）。第 1 天和第 5 天之间的 t1/2 值既不依赖于剂量也不依赖于时间表（平均 5.0 至 7.3 天）。快速输注 2 至 3 小时后，游离铂浓度呈双指数下降，但在 24 小时输注后，游离铂浓度呈单指数下降。最终 t1/2 值范围为 26.0 至 78.8 分钟。在肾功能和肝功能正常的患者中，当给予相同剂量时，不同持续时间的顺铂输注的游离铂AUC是相同的。游离铂清除率与肌酐清除率相关（P = 0.017）。红细胞中铂的吸收很快，并且峰值浓度与游离铂 AUC 相关（P = 0.0006），与输注时间表无关。红细胞中铂水平的衰减是双相的。第 5 天和第 15 天之间间隔的平均终末 t1/2 为 29.8 天。这表明顺铂给药导致红细胞分解。
Pharmacokinetic studies were performed in 51 patients who received cisplatin infusions. Two treatment regimens (single-day or daily for 5 days) and three infusion schedules (for 4 to 15 minutes, 2 to 3 hours or 24 hours) were used. The daily dose of cisplatin varied from 20 to 120 mg/m2. The kinetics of total platinum studied up to day 5 revealed differences only during the initial period after the infusion. Peak levels were both dose and schedule dependent and initial t12 values in the decay curves were only schedule dependent (mean values: 13 minutes for rapid infusions, 40.3 minutes for 2 to 3-hour infusions, and 220.5 minutes for 24-hour infusion). The t1/2 values between days 1 and 5 were neither dose nor schedule dependent (mean 5.0 to 7.3 days). Concentrations of free platinum declined biexponentially after the rapid and 2 to 3-hour infusions, but they declined monoexponentially after 24-hour infusions. Final t1/2 values ranged from 26.0 to 78.8 minutes. In patients with normal renal and hepatic function, the free platinum AUC was identical for cisplatin infusions of different duration when equal doses were given. Free platinum clearance correlated with creatinine clearance (P = 0.017). The uptake of platinum in red blood cells was rapid, and peak concentrations correlated with the free platinum AUC (P = 0.0006) independent of the infusion schedule. The decay of platinum levels in red blood cells was biphasic. The mean terminal t1/2 for the interval between days 5 and 15 was 29.8 days. This suggests a breakdown of red blood cells that results from cisplatin dosing.