Saini N K, Wasik B, Pires J, Leale D M, Quach N, Culp W T N, Samms R J, Johnson A E, Owens J G, Gilor C
Department of Veterinary Medicine and Epidemiology, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
Department of Veterinary Surgical and Radiological Sciences, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
Domest Anim Endocrinol. 2021 Apr;75:106595. doi: 10.1016/j.domaniend.2020.106595. Epub 2020 Nov 17.
Insulin glargine (IGla) is a synthetic human-recombinant insulin analog that is used routinely in people as a q24h basal insulin. The 300 U/mL (U300) formulation of IGla is associated with longer duration of action and less within-day variability, making it a better basal insulin compared with the 100 U/mL (U100) formulation. We hypothesized that in healthy cats, IGlaU300 has a flatter time-action profile and longer duration of action compared with IGlaU100. Seven healthy neutered male, purpose-bred cats were studied in a randomized, crossover design. Pharmacodynamics of IGlaU100 and IGlaU300 (0.8 U/kg, subcutaneous) were determined by the isoglycemic clamp method. The time-action profile of IGlaU300 was flatter compared with IGlaU100 as demonstrated by lower peak (5.6 ± 1.1 mg/kg/min vs 8.3 ± 1.9 mg/kg/min, respectively; P = 0.04) with no difference in total metabolic effect (ME; P = 0.7) or duration of action (16.8 h ± 4.7 h vs 13.4 h ± 2.6 h; P = 0.2). The greater fraction of ME in the 12- to 24-h period postinjection (35 ± 23% vs 7 ± 8% respectively; P = 0.048) and lower intraday GIR% variability (7.8 ± 3.7% vs 17.4 ± 8.2% respectively; P = 0.03) supports a flatter time-action profile of IGlaU300. There were no differences in onset and end of the action. In summary, although both formulations have a similar duration of action that is well below 24 h, the ME of IGlaU300 is more evenly distributed over a 24 h period in healthy cats, making it a better candidate for once-daily injection in diabetics compared with IGlaU100.
甘精胰岛素(IGla)是一种人工合成的重组人胰岛素类似物,通常作为基础胰岛素用于人体,每日一次皮下注射。与100 U/mL(U100)剂型相比,300 U/mL(U300)剂型的甘精胰岛素作用持续时间更长,日内变异性更小,是一种更好的基础胰岛素。我们假设,在健康猫中,与IGlaU100相比,IGlaU300的时效曲线更平缓,作用持续时间更长。采用随机交叉设计对7只健康的绝育雄性实验猫进行了研究。通过等血糖钳夹法测定IGlaU100和IGlaU300(0.8 U/kg,皮下注射)的药效学。与IGlaU100相比,IGlaU300的时效曲线更平缓,表现为峰值更低(分别为5.6±1.1 mg/kg/min和8.3±1.9 mg/kg/min;P=0.04),但总代谢效应(ME;P=0.7)或作用持续时间无差异(分别为16.8 h±4.7 h和13.4 h±2.6 h;P=0.2)。注射后12至24小时内ME的比例更高(分别为35±23%和7±8%;P=0.048),日内葡萄糖输注率(GIR%)变异性更低(分别为7.8±3.7%和17.4±8.2%;P=0.03),这支持了IGlaU300时效曲线更平缓的结论。作用的起效和结束时间无差异。总之,虽然两种剂型的作用持续时间相似且远低于24小时,但在健康猫中,IGlaU300的ME在24小时内分布更均匀,与IGlaU100相比,它更适合作为糖尿病猫每日一次注射的药物。