Effect of liver resection on the pharmacodynamics of gemcitabine hydrohloride

在大鼠部分肝切除模型中，给予推荐剂量的吉西他滨导致POD 2时的血药浓度高于非肝切除大鼠（1.24倍）。80%剂量给药可达到与非肝切除大鼠推荐剂量相似的血药浓度。然而，在POD 14完成肝再生后，需要推荐剂量以达到预期血药浓度。另一方面，在部分肝切除术的临床环境中，尽管肝脏体积减小，但给予推荐剂量的吉西他滨不会导致血药浓度过高。然而，与骨髓抑制相关的不良反应的发生率在肝切除术后的患者中更高。这些结果表明，肝切除术后对吉西他滨的耐受性降低并不仅仅是血液中吉西他滨药效学的原因。

In rat partial hepatectomy model, gemcitabine administration of recommended dose resulted in higher blood concentration (1.24 times) than non-hepatectomized rat on POD 2. Ad-ministration of 80% dose could achieve the blood concentration similar to that in nonhepatectomized rat received recommended dose. However, after completion of liver regeneration on POD 14, recommended dose was necessary to achieve the expecting blood concentration. On the other hand, in the clinical setting of partial hepatectomy, administration of recommended dose of gemcitabine did not cause an excessive blood concentration in spite of reduced liver volume. However, the incidence of an adverse effect relating to bone marrow suppression was higher in the patients after hepatectomy. These result suggest that reduced tolerance for gemcitabine following hepatectomy does not simply responsible for gemcitabine pharmacodynamics in the blood.