Hartmann Helmut, Baumgardt Thomas, Höchel Joachim
Institut für Veterinär-Physiologie, Fachbereich Veterinärmedizin, Freie Universität Berlin.
Berl Munch Tierarztl Wochenschr. 2006 Jan-Feb;119(1-2):62-7.
Established renal function tests for the quantitative determination of the glomerular filtration rate (GFR) in small animals by means of an exogenous clearance marker like creatinine are based on the intravenous or subcutaneous administration of the marker. In order to simplify performing the test, the suitability of the peroral administration of the marker substance was tested. Exogenous creatinine was administered to 17 Beagle dogs successively by the peroral (dose: 4 g/m2 BSA) and the subcutaneous route (dose: 2 g/m2 BSA). Both routes were tested sequentially in fasted and fed animals. In addition to the peroral administration of creatinine, the absorption marker D-Xylose (dose: 0.5 g/kg body weight) was given per os. Pharmacokinetic parameters were calculated based on serum concentration--time data of both markers. Maximum serum concentrations of the exogenous creatinine (C(max) = 1284 +/- 173 micromol/l) were observed 92 +/- 19 min post-dose (t(max)) in fasted dogs after peroral administration of creatinine. C(max) (956 +/- 209 micromol/l) and t(max) (67 +/- 13 min) were statistically significantly reduced in fed animals. The exogenous plasma clearance of creatinine was about 1/3 lower in fasted animals (94 +/- 15 ml/min/m2) than in fed ones (134 +/- 28 ml/min/m2). The apparent terminal disposition half-life of the exogenous creatinine showed mean values of about 170 min (fasted) and 200 min (fed). After peroral administration of D-Xylose, fasted animals showed higher C(max) (3.9 +/- 0.99 mmol/l) and t(max) values (60 +/- 18 min) than fed dogs (C(max) = 2.2 +/- 0.55 mmol/l, t(max) = 40 +/- 15 min). C(max) and t(max) did not differ between fed and fasted dogs after subcutaneous administration of creatinine. Creatinine clearance was again higher in fed (124 +/- 12.8 ml/min/m2) than in fasted dogs (104 +/- 9.0 ml/min/m2) after subcutaneous administration of the marker. The terminal disposition half-live was, however, similar with about 130-140 min. The route of administration (peroral vs. subcutaneous) did not influence the calculated clearance (no statistical significance when p < 0.01 is required). Creatinine in a dose of 4 g/m2 BSA can be administered by the peroral route of administration for assessing the GFR. For the quantitative determination of GFR standardized condition are required, i.e. animals have to be fasted for > or = 6 hours.
通过外源性清除标记物(如肌酐)定量测定小动物肾小球滤过率(GFR)的现有肾功能测试是基于标记物的静脉内或皮下给药。为了简化测试操作,对标记物的口服给药适用性进行了测试。对17只比格犬依次经口(剂量:4 g/m²体表面积)和皮下途径(剂量:2 g/m²体表面积)给予外源性肌酐。在禁食和进食的动物中依次测试了这两种给药途径。除了口服肌酐外,还经口给予吸收标记物D-木糖(剂量:0.5 g/kg体重)。根据两种标记物的血清浓度-时间数据计算药代动力学参数。经口给予肌酐后,禁食犬在给药后92±19分钟(t(max))观察到外源性肌酐的最大血清浓度(C(max)=1284±173 μmol/L)。进食动物的C(max)(956±209 μmol/L)和t(max)(67±13分钟)在统计学上显著降低。禁食动物中肌酐的外源性血浆清除率(94±15 ml/min/m²)比进食动物(134±28 ml/min/m²)低约1/3。外源性肌酐的表观终末处置半衰期在禁食时平均值约为170分钟,进食时约为200分钟。经口给予D-木糖后,禁食动物的C(max)(3.9±0.99 mmol/L)和t(max)值(60±18分钟)高于进食犬(C(max)=2.2±0.55 mmol/L,t(max)=40±15分钟)。皮下给予肌酐后,进食和禁食犬的C(max)和t(max)无差异。皮下给予标记物后,进食犬(124±12.8 ml/min/m²)的肌酐清除率再次高于禁食犬(104±9.0 ml/min/m²)。然而,终末处置半衰期相似,约为130 - 140分钟。给药途径(口服与皮下)不影响计算出的清除率(当要求p<0.01时无统计学意义)。4 g/m²体表面积剂量的肌酐可通过口服途径给药以评估GFR。对于GFR的定量测定,需要标准化条件,即动物必须禁食≥6小时。