Predicted and actual BCNU concentrations in normal rabbit brain during intraarterial and intravenous infusions.
Predicted and actual BCNU concentrations in normal rabbit brain during intraarterial and intravenous infusions.
复制标题
动脉内和静脉输注期间正常兔脑中的预测和实际 BCNU 浓度。
DOI：
10.1007/bf00177438
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发表时间：
1996
影响因子：
3.9
通讯作者：
Colvin,OM
中科院分区：
文献类型：
--
作者：
Hassenbusch,SJ;Anderson,JH;Colvin,OM
使用正常新西兰白色家兔比较动脉内（IA）或静脉内（IV）输注后BCNU的理论脑浓度（基于药代动力学模型）与实际实验浓度。脑肿瘤患者的IA输注治疗基于理论预测是有希望的，但临床有效性有限。实验测量的兔颈动脉流速（63.9 ± 3.4 ml/min）[平均值± 1 sem]和BCNU全身清除率（197 ± 10.2 ml/min）预测理论IA优势为4.1 ± 0.2。IA输注（20 mg/min/m2，持续15分钟）期间和输注后，BCNU的同侧脑浓度分别为：输注开始后5、10、15、25、35和45分钟，16.2 ± 2.9、19.0 ± 3.9、20.3 ± 2.8、4.8 ± 2.5、2.1 ± 1.5和1.7 ± 1.6 μg/gm脑。对侧半球（IA输注）相同时间点的平均浓度为：7.1 ± 1.8、9.0 ± 1.8、10.3 ± 0.7、4.2 ± 1.4、2.2 ± 1.2、2.0 ± 1.5 μg/gm脑。IV输注期间任一半球的浓度与IA输注期间对侧半球的浓度相似。同侧比较：IA输注期间和之后的对侧半球比率为：在相同时间点为3.2 ± 0.4、2.6 ± 0.3、2.2 ± 0.3、1.1 ± 0.3、1.0 ± 0.4和0.9 ± 0.3。尽管这些数据显示IA输注的药物浓度较高，但实际值远低于理论建模预测值。理论和实验结果之间的这种差异强调需要进一步研究原因和补救措施，以便IA治疗可以达到更好的药物浓度，毒性更小。
Normal New Zealand White rabbits were used to compare theoretical brain concentrations (based upon pharmacokinetic modeling) with actual experimental concentrations of BCNU following intraarterial (IA) or intravenous (IV) infusions. IA infusion therapy for brain tumor patients has been promising based upon theoretical predictions but of limited effectiveness clinically. Experimentally-measured rabbit carotid artery flow rates (63.9 ± 3.4 ml/min) [mean ± 1 sem] and BCNU systemic clearances (197 ± 10.2 ml/min) predicted a theoretical IA advantage of 4.1 ± 0.2. lpsilateral brain concentrations of BCNU during and after IA infusions (20 mg/min/m2over 15 minutes) were: 16.2 ± 2.9, 19.0 ± 3.9, 20.3 ± 2.8, 4.8 ± 2.5, 2.1 ± 1.5, and 1.7 ± 1.6 μg/gm brain at 5, 10, 15, 25, 35, and 45 minutes after infusion start. Mean concentrations at same time points in contralateral hemisphere (IA infusions) were: 7.1 ± 1.8, 9.0 ± 1.8, 10.3 ± 0.7, 4.2 ± 1.4, 2.2 ± 1.2, 2.0 ± 1.5 μg/gm brain. Concentrations in either hemisphere during IV infusions were similar to contralateral hemisphere during IA infusions. Comparison of ipsilateral: contralateral hemisphere ratios during and after IA infusions were: 3.2 ± 0.4, 2.6 ± 0.3, 2.2 ± 0.3, 1.1 ± 0.3, 1.0 ± 0.4, and 0.9 ± 0.3 at the same time points. Although these data show higher drug concentrations with IA infusions, actual values were considerably less than predicted by theoretical modeling. This discrepancy between theoretical and experimental results emphasizes need for further study of causes and remedies so that IA therapy can achieve better drug concentrations with less toxicity.