Muchmore Douglas B, Vaughn Daniel E
Halozyme Therapeutics, Inc, San Diego, California, USA.
J Diabetes Sci Technol. 2010 Mar 1;4(2):419-28. doi: 10.1177/193229681000400223.
For patients with type 1 or type 2 diabetes, achieving good glycemic control is critical for successful treatment outcomes. As many patients remain unable to reach glycemic goals with currently available rapid-acting analog insulins, ultrafast insulin products are being developed that provide an even faster pharmacokinetic profile compared with current rapid prandial insulin products. The overall strategy of these ultrafast insulin products is to better mimic the normal physiologic response to insulin that occurs in healthy individuals to further improve glycemic control. Recombinant human hyaluronidase (rHuPH20) is a genetically engineered soluble hyaluronidase approved by the U.S. Food and Drug Administration as an adjuvant to increase the absorption and dispersion of other injected drugs; mammalian hyaluronidases as a class have over 6 decades of clinical use supporting the safety and/or efficacy of hyaluronidase coadministration. Clinical findings have demonstrated that coadministration of rHuPH20 with insulin or an insulin analog achieved faster systemic absorption, reduced inter- and intrapatient variability of insulin absorption, and achieved faster metabolic effects compared with injection of either insulin formulation alone. The magnitude of this acceleration is similar to the incrementally faster absorption of prandial insulin analogs as compared with regular insulin. In addition, coadministration of rHuPH20 with regular insulin or insulin analog also improved the achievement of prandial glycemic targets. Thus, rHuPH20 coadministration shows promise as a method of establishing a more rapid insulin profile to prandial insulin in patients with diabetes and has the potential to yield substantial improvements in postprandial glycemic excursion.
对于1型或2型糖尿病患者，实现良好的血糖控制对于成功的治疗结果至关重要。由于许多患者使用目前可用的速效胰岛素类似物仍无法达到血糖目标，因此正在开发超快速胰岛素产品，与目前的速效餐时胰岛素产品相比，其药代动力学特征更快。这些超快速胰岛素产品的总体策略是更好地模拟健康个体中发生的对胰岛素的正常生理反应，以进一步改善血糖控制。重组人透明质酸酶（rHuPH20）是一种经美国食品药品监督管理局批准的基因工程可溶性透明质酸酶，作为佐剂可增加其他注射药物的吸收和扩散；作为一类的哺乳动物透明质酸酶已有60多年的临床使用历史，支持透明质酸酶联合给药的安全性和/或有效性。临床研究结果表明，与单独注射任何一种胰岛素制剂相比，rHuPH20与胰岛素或胰岛素类似物联合给药可实现更快的全身吸收，降低患者间和患者内胰岛素吸收的变异性，并实现更快的代谢效应。这种加速的程度与餐时胰岛素类似物比常规胰岛素更快的吸收增加相似。此外，rHuPH20与常规胰岛素或胰岛素类似物联合给药也改善了餐时血糖目标的实现。因此，rHuPH20联合给药有望作为一种在糖尿病患者中建立比餐时胰岛素更快的胰岛素谱的方法，并且有可能在餐后血糖波动方面取得实质性改善。
