Okumura K, Arakawa M, Hori R
J Pharm Sci. 1980 Feb;69(2):157-9. doi: 10.1002/jps.2600690210.
The distribution of sulfonylureas and their insulin-releasing potency as a pharmacological response were studied in isolated perfused rat pancreas. Sulfonylurea concentrations in the perfused pancreas in the presence or absence of a second drug were determined after perfusion for 15 min. Sulfonylureas could be distributed throughout the pancreas readily, and the tissue sulfonylurea concentration was reduced by the addition of sulfaphenazole, sulfadimethoxine, and salicylic acid. The insulin secretion rate stimulated by tolbutamide also was reduced by these three drugs; sulfanilamide, which could not displace the tolbutamide distribution, did not affect the tolbutamide-mediated secretion of insulin. These results document the importance of drug concentration in the tissue or receptor site with regard to insulin secretion and show that the sulfonylurea-mediated secretion of insulin can be modified easily by concomitant perfusion of a second drug that displaces sulfonylurea in the pancreas. These findings suggest that the drug interaction at the target organ or receptor site should be understood to provide adequate drug therapy.
在离体灌注大鼠胰腺中研究了磺脲类药物的分布及其作为药理反应的胰岛素释放效力。在灌注15分钟后，测定存在或不存在第二种药物时灌注胰腺中的磺脲类药物浓度。磺脲类药物可轻易分布于整个胰腺，添加磺胺苯吡唑、磺胺二甲氧嘧啶和水杨酸后，组织中的磺脲类药物浓度降低。这三种药物也降低了甲苯磺丁脲刺激的胰岛素分泌率；不能取代甲苯磺丁脲分布的磺胺对甲苯磺丁脲介导的胰岛素分泌没有影响。这些结果证明了组织或受体部位的药物浓度对胰岛素分泌的重要性，并表明通过同时灌注能取代胰腺中磺脲类药物的第二种药物，可轻易改变磺脲类药物介导的胰岛素分泌。这些发现表明，应了解靶器官或受体部位的药物相互作用，以提供充分的药物治疗。
