Impact of age-related alteration of plasma alpha 1-acid glycoprotein concentration on erythromycin pharmacokinetics in pigs.
Erythromycin (EM) pharmacokinetic variables were studied after IV administration of the drug (10 mg/kg of body weight) to 1-, 6-, and 15-day-old pigs. With advancing age, from 1 day to 15 days after birth, half-life of EM became shorter (3.0 hours to 1.4 hour), whereas apparent volume of distribution, total body clearance (CLt), and intrinsic clearance became greater: 0.68 to 3.28 (L/kg), 0.15 to 1.42 (L/h/kg), and 1.81 to 3.56 (L/h/kg), respectively. The percentage of plasma protein binding of EM decreased from 91 to 56%, correlating well with volume of distribution and CLt values. The altered binding percentage depended on plasma alpha 1-acid glycoprotein (AGP) concentration, but not on albumin concentration. With advancing age, plasma AGP concentration was markedly decreased from approximately 6,000 micrograms/ml to 700 micrograms/ml. Despite a twofold increase in intrinsic clearance with advancing age, CLt increased ninefold, implying that the decreased protein binding contributed to the increase of CLt more preferentially than did maturational development of elimination capacity. Therefore, the altered protein binding of EM attributable to the change in plasma AGP concentration could be a major causal factor of the age-related pharmacokinetic variables of EM in pigs.
Kinoshita
T
T
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Japan.
Son
D S
DS
Shimoda
M
M
Kokue
E
E
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004917:Erythromycin / Q000097:blood / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013552:Swine / Q000378:metabolism*
D009961:Orosomucoid; D012709:Serum Albumin; D004917:Erythromycin