Ho N F, Geary T G, Barsuhn C L, Sims S M, Thompson D P
Drug Delivery Systems Research, Upjohn Laboratories, Kalamazoo, MI 49001.
Mol Biochem Parasitol. 1992 May;52(1):1-13. doi: 10.1016/0166-6851(92)90031-e.
Using live, intact Ascaris suum and a closed perfusion system, the absorption kinetics and tissue distribution of selected radiolabeled permeants were measured to determine the importance of the transcuticular pathway for drug absorption. The data support the conclusions established by previous in vitro transport studies which utilized excised cuticle-hypocuticle tissue preparations. The external surface of A. suum can be breached by drugs and the rate-determining barrier is the lipoidal hypocuticle tissue, provided the permeant is sufficiently small to traverse the aqueous-filled, negatively charged collagen matrix of the cuticle. The ex vivo permeability coefficients of the model permeants for the cuticle-hypocuticle barrier were in good quantitative agreement with the in vitro permeability coefficients. The lipophilic permeants hydrocortisone and p-nitrophenol were preferentially distributed in the gut tissue, whereas the hydrophilic permeant urea was distributed evenly throughout the organism and was extensively metabolized. Ligated and nonligated A. suum showed no significant differences in either uptake kinetics or tissue distribution of the permeants. This indicates that the transcuticular pathway is the major route of drug absorption as compared to oral ingestion.
利用活的完整猪蛔虫和封闭灌注系统，测定了选定放射性标记渗透剂的吸收动力学和组织分布，以确定经皮途径对药物吸收的重要性。这些数据支持了先前利用切除的角质层-皮下组织制剂进行的体外转运研究所得出的结论。只要渗透剂足够小，能够穿过充满水的、带负电荷的角质层胶原基质，猪蛔虫的外表面就可以被药物穿透，限速屏障是脂质皮下组织。模型渗透剂对角质层-皮下屏障的离体渗透系数与体外渗透系数在数量上吻合良好。亲脂性渗透剂氢化可的松和对硝基苯酚优先分布在肠道组织中，而亲水性渗透剂尿素则均匀分布于整个生物体并被广泛代谢。结扎和未结扎的猪蛔虫在渗透剂的摄取动力学或组织分布上均无显著差异。这表明，与口服摄入相比，经皮途径是药物吸收的主要途径。
