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短小肠患者的肠内药物吸收:综述

Enteral drug absorption in patients with short small bowel : a review.

作者信息

Severijnen René, Bayat Nazila, Bakker Hans, Tolboom Jules, Bongaerts Ger

机构信息

Department of Paediatric Surgery, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.

出版信息

Clin Pharmacokinet. 2004;43(14):951-62. doi: 10.2165/00003088-200443140-00001.

Abstract

Drug therapy may become difficult when a significant amount of the small intestine is resected, as happens in patients with a short small bowel. Drug absorption from the gastrointestinal tract is altered in these patients; however, this effect is variable in patients and differs with each drug. Literature regarding clinical outcomes of normal or alternative administration routes in patients with a short small bowel is limited. We explored what is written about the normal absorption of commonly used drugs and what difference the resection of different but substantial parts of the small intestine makes. Changes in the gastrointestinal tract after resection of >50% of the small intestine causes malabsorption of macronutrients and micronutrients, and may alter the drug absorption process. The metabolic activity of the abundantly present intestinal lactobacilli can also affect the enteral drug absorption in patients with short small bowel as this results in the production of lactic acid, gaseous CO(2), ethanol and an increased bile acid deconjugation. Accelerated intestinal luminal transit time causes a reduction in absorption of certain antimicrobial agents, digoxin, hydrochlorothiazide, ciclosporin, cimetidine, mesalazine (5-aminosalicylic acid), oral contraceptives and levothyroxine. Gastric hypersecretion and lack of sufficient contact time with the intestinal mucosa in patients with short small bowel leads to insufficient absorption of drugs such as omeprazole. Successful treatment with warfarin, tricyclic antidepressants, metronidazole, fluconazole, procainamide, sotalol and pindolol are reported in several studies. Many different factors cause this variability in drug absorption in such patients. Monitoring the serum drug concentration in these patients may ease dealing with the management problems.

摘要

当大量小肠被切除时,药物治疗可能会变得困难,小肠短的患者就会出现这种情况。这些患者胃肠道的药物吸收会发生改变;然而,这种影响在患者中存在差异,且因药物而异。关于小肠短的患者正常或替代给药途径的临床结果的文献有限。我们探讨了关于常用药物正常吸收的相关内容,以及小肠不同但相当部分的切除会产生何种差异。切除超过50%的小肠后胃肠道的变化会导致大量营养素和微量营养素吸收不良,并可能改变药物吸收过程。大量存在的肠道乳酸杆菌的代谢活性也会影响小肠短的患者的肠内药物吸收,因为这会导致乳酸、气态二氧化碳、乙醇的产生以及胆汁酸去结合增加。肠道腔转运时间加快会导致某些抗菌药物、地高辛、氢氯噻嗪、环孢素、西咪替丁、美沙拉嗪(5-氨基水杨酸)、口服避孕药和左甲状腺素的吸收减少。小肠短的患者胃分泌过多以及与肠黏膜接触时间不足会导致奥美拉唑等药物吸收不足。几项研究报告了华法林、三环类抗抑郁药、甲硝唑、氟康唑、普鲁卡因胺、索他洛尔和吲哚洛尔的成功治疗案例。许多不同因素导致此类患者药物吸收的这种变异性。监测这些患者的血清药物浓度可能有助于解决管理问题。

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