Luzio S, Dunseath G, Peter R, Pauvaday V, Owens D R
Diabetes Research Unit, Llandough Hospital, Penlan Road, Penarth, South Glamorgan, CF64 2XX, UK.
Diabetologia. 2006 Jun;49(6):1163-8. doi: 10.1007/s00125-006-0243-2. Epub 2006 Apr 5.
AIMS/HYPOTHESIS: The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared.
Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured.
All 12 patients were men; mean (+/-SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m2 and HbA(1c) 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3-5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2-3 h. A flatter plasma insulin profile reached a plateau approximately 6-16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection.
CONCLUSIONS/INTERPRETATION: The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.
目的/假设:比较双相门冬胰岛素(BIAsp 30)(30%可溶性,70%精蛋白门冬胰岛素[IAsp])和甘精胰岛素(IGlarg)的药代动力学和药效学特性。
12名2型糖尿病患者参加了两项间隔1周的24小时等血糖钳夹研究。患者被随机分为接受0.5 U/kg的BIAsp 30治疗(08:30时0.25 U/kg,20:30时0.25 U/kg)或08:30时0.50 U/kg的IGlarg治疗。两种胰岛素均通过皮下注射至前腹壁。测量血浆葡萄糖、葡萄糖输注速率、血浆胰岛素和C肽浓度。
所有12名患者均为男性;平均(±标准差)年龄为58.8(8.9)岁,体重指数为31.0(3.0)kg/m²,糖化血红蛋白为7.1(0.6)%。在24小时钳夹期内血浆葡萄糖保持恒定。每次注射BIAsp 30后,葡萄糖输注速率增加,在注射后约3 - 5小时达到明显峰值。注射IGlarg后观察到的注射后曲线则较为平缓。每次注射BIAsp 30后血浆胰岛素浓度迅速上升,在约2 - 3小时后达到明显峰值。注射IGlarg后血浆胰岛素曲线较为平缓,在约6 - 16小时后达到平台期。两次注射BIAsp 30后血浆C肽均降至基线以下,但注射IGlarg后保持不变。
结论/解读:以两次分剂量给予等效剂量(0.5 U/kg)的BIAsp 30后的药效学和药代动力学曲线分别比每日单次剂量给予IGlarg时高34%和28%。