Bawdon R E
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas 75235-9032, USA.
Infect Dis Obstet Gynecol. 1998;6(6):244-6. doi: 10.1002/(SICI)1098-0997(1998)6:6<244::AID-IDOG4>3.0.CO;2-B.
The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model.
The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography.
The clearance index of abacavir was 0.47 +/- 0.19 and 0.50 +/- 0.07 at peak and trough concentrations, respectively. The clearance index of amprenavir was 0.38 +/- 0.09 and 0.14 +/- 0.08 at peak and trough concentrations, respectively. There was no unusual accumulation of either drug in the media or tissue when the perfusion system was closed.
Abacavir is the first nucleoside compound studied in the perfusion system with a high clearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 times greater than the clearance index of ritonavir at peak concentration determined in a previous study. At trough concentration the clearance index was much less than at the peak concentration. A similar result was found with ritonavir.
在体外人胎盘模型中研究了用于治疗人类免疫缺陷病毒的新型核苷抑制剂阿巴卡韦和新型蛋白酶抑制剂安普那韦的转运情况。
体外人胎盘模型使用C14安替比林来确定这些化合物在血清浓度峰值和谷值时的转运分数和清除指数。通过高压液相色谱法测定每种药物的清除指数累积和组织浓度。
阿巴卡韦在峰值和谷值浓度时的清除指数分别为0.47±0.19和0.50±0.07。安普那韦在峰值和谷值浓度时的清除指数分别为0.38±0.09和0.14±0.08。当灌注系统关闭时，两种药物在培养基或组织中均未出现异常蓄积。
阿巴卡韦是在灌注系统中研究的第一种具有高清除指数的核苷化合物。蛋白酶抑制剂安普那韦的转运在峰值浓度时的清除指数比先前研究中测定的利托那韦的清除指数大2.75倍。在谷值浓度时，清除指数远低于峰值浓度。利托那韦也有类似结果。
