The pharmacokinetics of γ‐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 statistically 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.