Colonic absorption of antiepileptic agents.
Colonic absorption of antiepileptic agents.
复制标题
抗癫痫药的结肠吸收。
DOI：
10.1111/j.1528-1157.1997.tb01078.x
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发表时间：
1997
期刊：
影响因子：
5.6
通讯作者：
Fleisher,D
中科院分区：
文献类型：
--
作者：
Stevenson,CM;Kim,J;Fleisher,D
目的：评价用于研究药物结肠吸收的犬肠道入口模型。抗癫痫药物苯妥英钠和加巴喷丁被选择来研究吸收的亲脂性和亲水性compounds.Methods：药物的血浆浓度-时间图产生后，小肠和结肠给药的两种药物。以两种剂量给予水溶性差的苯妥英，以评价溶出速率限度对结肠吸收的影响。最大血浆浓度（Cmax）和血浆水平-时间曲线（AUC）下的面积被用来评估结肠吸收血浆level.Results的相对贡献：而结肠加巴喷丁AUC和Cmax仅为0.25和0.15小肠给药后，结肠苯妥英AUC和Cmax的一半，分别相当于小肠给药观察到的。此外，结肠给药较高的苯妥英剂量表现出次要的最大值和持续增加的药物血浆levels with time.Conclusions：结肠的加巴喷丁吸收是穷人相比，上肠吸收，符合膜转运率限制这种亲水性AED的吸收。结肠和小肠给药的苯妥英血浆峰水平相当，表明膜转运不会限制这种亲脂性药物的吸收。较高苯妥英剂量导致的血浆水平持续升高与结肠中药物吸收的溶出速率控制一致。我们认为，结肠吸收提供了一个更大的潜在毒性苯妥英过量作为一个功能的持续药物溶解比加巴喷丁过量。
Purpose:To evaluate a canine intestinal access‐port model to study colonic absorption of drugs. The antiepileptic drugs phenytoin and gabapentin were chosen to study absorption of a lipophilic and hydrophilic compound, respectively.Methods:Drug plasma level—time plots were generated subsequent to small intestinal and colonic drug administration of both drugs. The poorly water‐soluble phenytoin was administered in two doses to evaluate the impact of dissolution rate limits on colonic absorption. Maximal plasma concentration (Cmax) and area under the plasma level‐time curve (AUC) were used to assess the relative contribution of colonic absorption to plasma levels.Results:Whereas colonic gabapentin AUC and Cmaxwere only 0.25 and 0.15 of those seen after small intestinal administration, colonic phenytoin AUC and Cmaxwere one half and equivalent to, respectively, those observed for small intestinal administration. Furthermore, colonic administration of a higher phenytoin dose showed secondary maxima and continued increases in drug plasma levels with time.Conclusions:Colonic gabapentin absorption is poor compared with upper intestinal absorption, consistent with membrane transport rate limits to the absorption of this hydrophilic AED. Peak phenytoin plasma levels from colonic and small intestinal administration are comparable, indicating membrane transport does not limit absorption of this lipophilic agent. Continued plasma‐level increases from higher phenytoin doses are consistent with dissolution‐rate control of drug absorption in the colon. We suggest that colonic absorption provides a greater potential for toxicity from phenytoin overdose as a function of continued drug dissolution than for gabapentin overdose.