[Suitability of the peroral administration of the marker creatinine for the quantitative determination of the glomerular filtration rate (GFR) in dogs].
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.
Hartmann
Helmut
H
Institut für Veterinär-Physiologie, Fachbereich Veterinärmedizin, Freie Universität Berlin. hehart@zedat.fu-berlin.de
Baumgardt
Thomas
T
Höchel
Joachim
J
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004285:Dogs / Q000378:metabolism*; D005215:Fasting; D005260:Female; D005919:Glomerular Filtration Rate / Q000662:veterinary*; D007279:Injections, Subcutaneous / Q000662:veterinary; D007677:Kidney Function Tests / Q000379:methods / Q000662:veterinary; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D012016:Reference Values
D003404:Creatinine