MECHANISTIC STUDIES IN THE TRANSCUTICULAR DELIVERY OF ANTIPARASITIC DRUGS .2. EXVIVO INVITRO CORRELATION OF SOLUTE TRANSPORT BY ASCARIS-SUUM
MECHANISTIC STUDIES IN THE TRANSCUTICULAR DELIVERY OF ANTIPARASITIC DRUGS .2. EXVIVO INVITRO CORRELATION OF SOLUTE TRANSPORT BY ASCARIS-SUUM
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DOI：
10.1016/0166-6851(92)90031-e
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发表时间：
1992-05-01
影响因子：
1.5
通讯作者：
THOMPSON, DP
中科院分区：
文献类型：
--
作者：
HO, NFH;GEARY, TG;THOMPSON, DP
使用活的、完整的猪蛔虫和封闭的灌注系统，测量了选定的放射性标记渗透剂的吸收动力学和组织分布，以确定经表皮途径对药物吸收的重要性。该数据支持先前利用切除角质层-下角质层组织制备的体外转运研究所建立的结论。荷叶草的外表面可以被药物破坏，其速率决定屏障是脂质角质层下组织，前提是渗透物足够小，可以穿过充满水的、带负电荷的角质层胶原基质。模型渗透剂对角质层-下角质层屏障的体外渗透系数与体外渗透系数有较好的定量一致性。亲脂性渗透物氢化可的松和对硝基酚优先分布在肠道组织中，而亲水渗透物尿素则均匀分布在机体内并被广泛代谢。结扎和未结扎的水草在渗透剂的摄取动力学和组织分布方面没有显著差异。这表明与口服摄入相比，经表皮途径是药物吸收的主要途径。
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.