Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain.
Int J Pharm. 2010 Mar 30;388(1-2):175-80. doi: 10.1016/j.ijpharm.2009.12.054. Epub 2010 Jan 7.
This paper presents the pharmacokinetic of human growth hormone (hGH) implantable tablets tested on a human ovarian cancer mouse model. In order to obtain a sustained release device which permits to administer a high dose of the hormone that keeps its integrity and stability, three different formulations of hGH-poly (d,l-lactic-co-glycolic acid) (PLGA) were elaborated by direct compression method varying hormone load, PLGA content and compactation time. In vitro studies showed that drug release was mainly controlled by hormone load. Pharmacokinetic studies were conducted by using immunodeficient female mice. Four days before the insertion of hGH implantable tablets in the peritoneal cavity, every mouse received 5x10(6) human ovarian cancer cells (SKOV3.ip1). Hormone serum levels were monitored through bleeding from eye orbital vessels. The population pharmacokinetic model used was based on the in series tank model and model parameters were estimated using the maximum likelihood method. The null hypothesis test about differences between formulations leads us to the conclusion that the three formulations showed the same kinetic behavior except for the hGH load. The hormone release was extended all over 2 weeks but no increase or decrease in survival time was observed. These results suggest that hGH serum levels do not facilitate tumoral cells proliferation, an expected effect of hGH and this could explain why survival times of mice treated with implantable tablets are not shorter than those treated with the control ones.
本文介绍了在人卵巢癌细胞模型中测试的可植入人重组生长激素（hGH）片剂的药代动力学。为了获得一种能够给予高剂量激素的持续释放装置，该激素保持其完整性和稳定性，通过直接压缩法制备了三种不同配方的 hGH-聚（丙交酯-乙交酯）（PLGA），其变化因素包括激素负载、PLGA 含量和压实时间。体外研究表明，药物释放主要由激素负载控制。通过免疫缺陷雌性小鼠进行药代动力学研究。在将 hGH 可植入片剂插入腹腔前 4 天，每只小鼠接受 5x10(6)个人卵巢癌细胞（SKOV3.ip1）。通过眼眶血管采血监测激素血清水平。使用的群体药代动力学模型基于串联罐模型，模型参数通过最大似然法进行估计。关于配方之间差异的零假设检验使我们得出结论，除了 hGH 负载外，三种配方表现出相同的动力学行为。激素释放持续了整整 2 周，但未观察到存活时间的增加或减少。这些结果表明，hGH 血清水平不会促进肿瘤细胞增殖，这是 hGH 的预期作用，这可以解释为什么接受可植入片剂治疗的小鼠的存活时间不比接受对照治疗的小鼠短。
