Michels G M, Boudinot F D, Ferguson D C, Hoenig M
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Am J Vet Res. 1999 Jun;60(6):738-42.
To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.
6 healthy adult ovariohysterectomized cats.
In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography.
Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean +/- SD) 11.5+/-4.2 hours. Metformin was distributed to a small central compartment of 0.057+/-0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12+/-0.02 and 0.37+/-0.38 L/kg. Steady-state volume of distribution was 0.55+/-0.38 L/kg. After IV administration, 84+/-14% of the dose was excreted unchanged in urine, with renal clearance of 0.13+/-0.03 L/h/kg; nonrenal clearance was negligible (0.02+/-0.02 L/kg). Mean bioavailability of orally administered metformin was 48%.
The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction.
On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans.
确定单剂量静脉注射和口服二甲双胍后，其在健康猫体内的药代动力学。
6只健康成年去势绝育猫。
在一项随机交叉设计研究中，每只猫静脉注射和口服25mg二甲双胍/千克体重。给药后采集血液和尿液样本，采用高效液相色谱法测定血浆和尿液中二甲双胍的浓度。
药物处置符合三室模型，终末相半衰期为（均值±标准差）11.5±4.2小时。二甲双胍分布于一个较小的中央室，容积为0.057±0.017L/kg，以及两个外周室，分布容积分别为0.12±0.02和0.37±0.38L/kg。稳态分布容积为0.55±0.38L/kg。静脉注射后，84±14%的剂量以原形经尿液排泄，肾脏清除率为0.13±0.03L/（小时·千克）；非肾脏清除率可忽略不计（0.02±0.02L/kg）。口服二甲双胍的平均生物利用度为48%。
二甲双胍在猫体内的总体处置模式与人类报道的相似。二甲双胍主要通过肾脏清除；因此，该药物不应在有严重肾功能不全的猫中使用。
根据我们的结果，计算机模拟表明，每12小时给猫口服2mg二甲双胍/千克，将产生在人类中已证明有效的血浆浓度。
