title: Pharmacokinetics of erythropoietin in intact and anephric dogs.
abstract: The present studies were performed to determine the pharmacokinetic parameters of erythropoietin in intact and anephric dogs by use of unlabeled crude native erythropoietin (nEp) and iodine 125-labeled purified recombinant erythropoietin (rEp) given by intravenous infusion for 15 minutes. Sephadex G-75 gel filtration was used to confirm that the 125I-rEp molecule remained iodinated in dog plasma during the 24-hour period of these studies. The plasma disappearance of erythropoietin conformed to a biexponential equation for both nEp and 125I-rEp, with the central compartment being larger than the peripheral compartment. The mean distribution half-life of 75.3 +/- 21.2 minutes for nEp was significantly (p less than 0.05) longer than that of 125I-rEp (23.7 +/- 5.0 minutes) in intact dogs. The intercompartmental clearance (CIic) for nEp (0.018 +/- 0.006 L/kg/hr) was significantly smaller than that of 125I-rEp (0.068 +/- 0.018 L/kg/hr) in intact dogs (p less than 0.05). There were no significant differences in apparent volume of distribution, elimination half-life, and elimination clearance (CIe) for nEp and rEp in intact dogs. The mean elimination half-life for 125I-rEp in intact dogs (9.0 +/- 0.6 hours) and anephric dogs (13.8 +/- 1.4 hours) was significantly different (p less than 0.05). The CIe for 125I-rEp in anephric dogs (0.008 +/- 0.001 L/kg/hr) was significantly (p less than 0.05) smaller than that of 125I-rEp in intact dogs (0.011 +/- 0.001 L/kg/hr). There were no significant differences in apparent volume of distribution, distribution half-life, and CIic for 125I-rEp in intact and anephric dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
authors: J S
authors: JS
authors: Fu
authors: J J
authors: JJ
authors: Lertora
authors: J
authors: J
authors: Brookins
authors: J C
authors: JC
authors: Rice
authors: J W
authors: JW
authors: Fisher
mesh_terms: D000818:Animals; D002850:Chromatography, Gel; D004285:Dogs / Q000378:metabolism*; D004921:Erythropoietin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D007457:Iodine Radioisotopes; D009399:Nephrons / Q000502:physiology*; D011863:Radioimmunoassay; D011994:Recombinant Proteins
chemical_list: D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004921:Erythropoietin