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The pharmacokinetics of γ‐glutamyl‐ l ‐dopa in normal and anephric rats and rats with glycerol‐induced acute renal failure
Author(s) -
Boateng Yaw A.,
Barber Harold E.,
MacDonald Thomas M.,
Petrie James C.,
Lee Michael R.,
Whiting Paul H.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12705.x
Subject(s) - pharmacokinetics , metabolite , volume of distribution , elimination rate constant , metabolism , chemistry , endocrinology , medicine , pharmacology , active metabolite , kidney , half life
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.