Slama G, Alamowitch C, Desplanque N, Letanoux M, Zirinis P
Department of Diabetes, Hôtel-Dieu Hospital, Paris, France.
Diabetologia. 1990 Nov;33(11):671-4. doi: 10.1007/BF00400568.
The main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 (insulin-dependent) diabetic patients. We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v. insulin-induced hypoglycaemia in diabetic patients. However, bioavailability and stability needed to be improved before intranasal glucagon could be introduced into clinical practice. This has now been achieved with a freeze-dried mixture of glucagon (1 mg) and glycocholic acid (1 mg) as a surfactant. Kinetics and efficacy have been controlled by (1) comparing subcutaneous and intranasal glucagon in 12 healthy non-hypoglycaemic subjects; (2) testing intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by an i.v. bolus of insulin and (3) comparing subcutaneous and intranasal glucagon in six Type 1 diabetic patients in whom hypoglycaemia was induced by adding extra subcutaneous regular insulin to their usual morning dosage. Our results show that 1 mg of intranasal glucagon is as effective as 1 mg of subcutaneous glucagon in terms of the rise in blood glucose. Differences in kinetics between the subcutaneous and the intranasal routes may be observed: intranasal glucagon initiates the blood glucose rise earlier than does the subcutaneous form but the effect of the latter is more sustained. Glycocholic acid appears to be a perfectly tolerated agent in acute conditions. The use of intranasal lyophylized glucagon, for the reversal of hypoglycaemia in Type 1 diabetes, seems to be a clinically relevant alternative to its parenteral equivalent and should now be ready to be introduced in the market.
胰高血糖素的主要治疗适应证是治疗1型（胰岛素依赖型）糖尿病患者胰岛素过量所致的低血糖。我们之前已经表明，一种含有7.5毫克胰高血糖素并以脱氧胆酸作为表面活性剂的鼻内喷雾剂能够纠正糖尿病患者静脉注射胰岛素所致的低血糖。然而，在鼻内胰高血糖素能够引入临床实践之前，其生物利用度和稳定性需要得到改善。现在，通过以胰高血糖素（1毫克）和甘氨胆酸（1毫克）作为表面活性剂的冻干混合物已经实现了这一点。通过以下方式控制了动力学和疗效：（1）在12名健康的非低血糖受试者中比较皮下注射和鼻内注射胰高血糖素；（2）在6名1型糖尿病患者中测试鼻内胰高血糖素，这些患者通过静脉推注胰岛素诱导低血糖；（3）在6名1型糖尿病患者中比较皮下注射和鼻内注射胰高血糖素，这些患者通过在其常规早晨剂量基础上额外皮下注射常规胰岛素诱导低血糖。我们的结果表明，就血糖升高而言，1毫克鼻内胰高血糖素与1毫克皮下注射胰高血糖素同样有效。皮下和鼻内给药途径之间的动力学差异可能会被观察到：鼻内胰高血糖素比皮下形式更早引发血糖升高，但后者的作用更持久。在急性情况下，甘氨胆酸似乎是一种耐受性良好的药物。使用鼻内冻干胰高血糖素逆转1型糖尿病患者的低血糖，似乎是其肠胃外等效物在临床上的一个相关替代方案，现在应该准备好投放市场。
