Leyvraz S, Hess U, Flesch G, Bauer J, Hauffe S, Ford J M, Burckhardt P
Centre Pluridisciplinaire d'Oncologie, University Hospital Lausanne, Switzerland.
J Natl Cancer Inst. 1992 May 20;84(10):788-92. doi: 10.1093/jnci/84.10.788.
Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients.
To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases.
Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine.
The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity.
The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.
帕米膦酸是一种第二代双膦酸盐，用于治疗肿瘤引起的高钙血症以及管理乳腺癌、骨髓瘤或前列腺癌的骨转移。癌症患者中帕米膦酸的药代动力学尚不清楚。
为确定给药速率和骨代谢的影响，我们研究了37例骨转移患者在三种不同输注速率下帕米膦酸的药代动力学。
将11 - 14例患者分为三组，分别在1小时、4小时或24小时内静脉输注60毫克帕米膦酸。收集三组患者的尿液样本。仅在1小时输注组采集血浆样本。用荧光胺对帕米膦酸进行衍生化后，通过高效液相色谱 - 荧光检测法测定血浆和尿液中的帕米膦酸。
帕米膦酸在0 - 24小时的体内潴留量（BR）占给药剂量的60% - 70%，且不受输注速率的显著影响。特别是在最快输注速率下，0 - 24小时的BR并未降低。患者之间，0 - 24小时的BR存在三倍的变异性，这直接与骨转移数量相关，在一定程度上也与肌酐清除率有关。在60毫克/小时时，血浆动力学呈多指数过程，其特征为分布相短。分布相的平均（±标准差）半衰期为0.8小时（±0.3），0 - 24小时血浆药物浓度 - 时间曲线下面积的平均（±标准差）为22.0±8.8微摩尔/升·小时，血浆最大浓度的平均（±标准差）为9.7微摩尔/升（±3.2）。对4例患者重复输注后，药代动力学变量保持不变。临床上，三种输注速率的耐受性相同，均无明显毒性。
对于转移性骨病患者，1小时输注速率在动力学上可能适合帕米膦酸的给药。
