PHARMACOKINETICS OF ERYTHROPOIETIN IN INTACT AND ANEPHRIC DOGS

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  • 1 June 1988
    • journal article
    • research article
    • Vol. 111  (6) , 669-676
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 < 0.05) longer than of 125I-rEp (23.7 .+-. 5.0 minutes) in intact dogs. The intercompartmental clearance (Clic) 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 < 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 < 0.05). The Cle for 125I-rEp in anephric dogs (0.008 .+-. 0.001 L/kg/hr) was significantly (p < 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 Cllc for 125I-rEp in the intact and anephric dogs. These studies indicate that (1) the pharmacokinetics of erythropoietin conform to a two-compartment model, with a central compartment volume of distribution that is larger than that of the peripheral compartment; (2) unlabeled nEp has a slower distribution rate than 125I-rEp, possibly attributable to aggregation of nEp; and (3) the kidney contributes significantly to the elimination clearance of erythropoietin.