THE PHARMACOKINETICS OF GAMMA-GLUTAMYL-L-DOPA IN NORMAL AND ANEPHRIC RATS AND RATS WITH GLYCEROL-INDUCED ACUTE-RENAL-FAILURE

1. The pharmacokinetics of γ-glutamyl-L-dopa (gludopa) and its metabolite, L-dopa, have been studied in normal rats at three dose levels of gludopa: 2 mg kg-1, 5 mg kg-1, and 7.5 mg kg-1. The extent of metabolism in normal rats, and the pharmacokinetics in anephric rats and rats with glycerol-induced acute renal failure (ARF) were also studied at a gludopa dose of 2 mg kg-1. 2. Gludopa was extensively metabolised to L-dopa with only about 10% of an injected dose being excreted unchanged. Normal rats had a rapid gludopa clearance of 50.9 ± 9.6 ml min-1 kg-1 and elimination rate constant of 2.99 ± 0.27 h-1. The mean residence time and half-life were 20.9 ± 1.4 and 14.4 ± 1.0 min, respectively. The apparent volume of distribution at steady state was 1.05 ± 0.181 kg-1. 3. No statistical significant differences were found in the main pharmacokinetic parameters between ARF and controls for either gludopa or its metabolite L-dopa. 4. In anephric rats and controls the kidneys were found to contribute about 68.5% and 67.2% to the elimination of gludopa and the metabolite L-dopa, respectively. 5. These results confirm that gludopa is an efficient pro-drug for L-dopa, and that the kidneys are the major site of gludopa metabolism. It seems likely that the renal specificity of gludopa persists in ARF.