Pharmacokinetics and toxicity of high-dose human alpha sub(1)-acid glycoprotein infusion in the rat

The pharmacokinetics of high-dose human alpha sub(1)-acid glycoprotein (AAG) was studied in rats to determine the feasibility of using AAG to alter the tissue distribution of basic drugs. alpha sub(1)-Acid glycoprotein was administered iv to six male Holtzman rats over 30 min, and serum AAG concentrations were measured by a radial immunodiffusion assay. The AAG concentrations were computer fit to a biexponential equation to generate pharmacokinetic constants for an open two-compartment model. The peak serum AAG concentration was 1830 mg/dL at the end of infusion; > 20 times the normal value for rats. The central volume of distribution and steady state volume of distribution were 0.09 and 0.15 L/kg, respectively.