Pharmacokinetics of erythropoietin in intact and anephric dogs.
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)
Fu
J S
JS
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Lertora
J J
JJ
Brookins
J
J
Rice
J C
JC
Fisher
J W
JW
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
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004921:Erythropoietin