Renal clearance of domoic acid in the rat

The renal clearance (Cl r) of the seafood toxin domoic acid (DA) was investigated in the rat. Following cannulation of the right femoral artery, the left femoral vein and the bladder of anaesthetized rats, a single bolus injection of either [ 3H]DA, [ 14C] p-aminohippuric acid (PAH) or [ 3H]inulin was administered through the venous cannula. Blood samples were taken from the arterial cannula at 1, 2, 10, 30, 50, 70, 90, 110 and 130 min following injection, and urine samples were collected at 20-min intervals starting from the time of bolus injection. Based on plasma concentration time profiles, the total clearances (Cl t) for DA, PAH and inulin were 9.12, 33.17 and 7.50 ml/min/kg body weight, respectively. The Cl r calculated from urinary excretion rates were not significantly different from the Cl t. Probenecid significantly reduced the Cl r of PAH but did not affect that of DA. When DA was given at doses of 0.5 ng, 0.5 mg and 2.0 mg/kg body weight, the pharmacokinetic parameters Cl t, Cl r, elimination-rate constant and apparent volume of distribution at steady state were not statistically different between doses. The entire dose of 3H was recovered in the urine by 160 min after dosing, and analysis of urine samples by HPLC confirmed that the radiolabel ( 3H) was associated predominantly with the parent form of DA. The results of the present study demonstrate that DA is cleared from plasma primarily through the kidneys. DA clearance occurs primarily by renal glomerular filtration since its Cl t is comparable with that of inulin, is less than that of PAH and is not affected by probenecid.