Kinetic analysis of the elimination process of human epidermal growth factor (hEGF) in rats.

Abstract Pharmacokinetic study of human epidermal growth factor (hEGF) in rats was performed in vivo . The hepatic extraction ratio ( E H ) of [ 125 I]hEGF, determined from the difference between the artery and the hepatic vein plasma concentrations at steady state, was 0.19. The hepatic clearance ( CL H : 7.56 ml/min/kg body wt), calculated by multiplying ( E H ) by the hepatic plasma flow rate ( Q P , H ), was approximately 70% of the total body clearance ( CL tot : 10.8 ml/min/kg body wt), which was determined from the steady-state arterial plasma concentration and the infusion rate. These results indicated that the liver is the main organ responsible for the removal of [ 125 I]hEGF from the systemic circulation in rats. The renal extraction ratio ( E R ) of [ 125 I]hEGF was half of that of [ 14 C]inulin; this may have resulted from the plasma protein binding of [ 125 I]hEGF, which was approximately 50% as determined by the charcoal adsorption method and the equilibrium gel-filtration method. The renal clearance ( CL R : 2.65 ml/min/kg body wt), calculated by multiplying E R by the renal plasma flow rate ( Q PR ), was approximately 17% of the CL tot - (15.6 ml/min/kg body wt), indicating a minor contribution of CL R . to CL tot compared with that of CL H to CL tot . The CL R of [ 125 I]hEGF calculated from the urinary excretion data was one-tenth of that calculated from the plasma concentration difference between the femoral artery and the renal vein at steady state. These results suggest that the bulk of [ 125 I]hEGF cleared from the plasma by the kidney may have been metabolized further in the renal tubules before appearing in the urine.