Tinworth Kellie D, Edwards Scott, Noble Glenys K, Harris Patricia A, Sillence Martin N, Hackett L Peter
School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia.
Am J Vet Res. 2010 Oct;71(10):1201-6. doi: 10.2460/ajvr.71.10.1201.
To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies.
8 IR ponies.
Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 days, and blood samples were obtained every 2 days. Plasma concentration at steady state (Css) was determined.
Mean±SD elimination half-life (t1/2) of metformin was 11.7±5.2 hours, maxima plasma concentration was 748±269 ng/mL at 54±32 minutes, mean area under the curve was 355±92 microg.h/mL, and apparent clearance was 90.6±28.1 mL/min/kg. The Css was 122±22 ng/mL.
Metformin reportedly enhances insulin sensitivity of peripheral tissues without stimulating insulin secretion, but bioavailability in horses is low. The t1/2 of metformin in IR ponies was similar to that in humans. Actual clearance of metformin adjusted for bioavailability in IR ponies was similar to that in humans; however, during chronic oral administration at dosages reported in efficacy studies, the Css of metformin was less than values associated with therapeutic efficacy in humans The apparent lack of long-term efficacy of metformin in horses is likely attributable to low bioavailability, rather than to rapid clearance.
确定胰岛素抵抗（IR）小马口服或鼻胃管给药后二甲双胍的药代动力学和血浆稳态动力学。
8匹IR小马。
通过鼻胃管给8匹小马服用二甲双胍（30mg/kg）。在24小时内定期采集血样。通过液相色谱 - 电喷雾串联质谱法测量血浆中二甲双胍的浓度。通过非房室分析确定药代动力学变量。给4匹小马额外连续20天每天两次（上午8点和下午5点）口服二甲双胍（15mg/kg），每2天采集血样。测定稳态时的血浆浓度（Css）。
二甲双胍的平均±标准差消除半衰期（t1/2）为11.7±5.2小时，最大血浆浓度在54±32分钟时为748±269ng/mL，平均曲线下面积为355±92μg·h/mL，表观清除率为90.6±28.1mL/min/kg。Css为122±22ng/mL。
据报道，二甲双胍可增强外周组织的胰岛素敏感性而不刺激胰岛素分泌，但在马体内的生物利用度较低。IR小马体内二甲双胍的t1/2与人类相似。根据生物利用度调整后，IR小马体内二甲双胍的实际清除率与人类相似；然而，在按照疗效研究中报道的剂量进行长期口服给药时，二甲双胍的Css低于与人类治疗效果相关的值。二甲双胍在马体内明显缺乏长期疗效可能归因于生物利用度低，而非清除迅速。
