Julius Justin M, Tindall Andrew, Moise Kenneth J, Refuerzo Jerrie S, Berens Pamela D, Smith Judith A
Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Reprod Toxicol. 2014 Nov;49:43-7. doi: 10.1016/j.reprotox.2014.06.003. Epub 2014 Jul 11.
The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL). To assess drug transfer and accumulation, samples were collected from maternal and fetal compartments. In the 50ng/mL open model, the mean transport fraction was 0.21±0.08 with clearance index of 0.53±0.66. Fetal peak concentrations achieved was 5.6±6.6ng/mL with mean accumulation of 5.35±6.4ng/mL. No drug was detected in the fetal compartment with the 5ng/mL models. Transplacental passage of granisetron was inconsistent at the 50ng/mL concentration that achieved with IV dosing. However, there consistently was no detectable passage in all the placentas evaluated of the granisetron at 5ng/mL concentration that would be achieved after transdermal patch administration.
本研究的目的是在离体胎盘灌注模型中评估格拉司琼的母胎经胎盘转运情况。足月人胎盘（N = 8）在分娩后立即收集。从每个胎盘取一个小叶，灌注格拉司琼浓度以模拟静脉注射（50ng/mL）或经皮给药（5ng/mL）后母体全身血浆峰值浓度。为评估药物转运和蓄积情况，从母体和胎儿隔室采集样本。在50ng/mL开放模型中，平均转运分数为0.21±0.08，清除指数为0.53±0.66。胎儿达到的峰值浓度为5.6±6.6ng/mL，平均蓄积量为5.35±6.4ng/mL。在5ng/mL模型的胎儿隔室中未检测到药物。静脉给药达到的50ng/mL浓度时，格拉司琼的经胎盘转运不一致。然而，在经皮贴剂给药后达到的5ng/mL浓度下，评估的所有胎盘中始终未检测到格拉司琼的转运。
