Abstract |
1. The pharmacokinetics of gamma-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 +/- 0.18 l 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.
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Authors | Y A Boateng, H E Barber, T M MacDonald, J C Petrie, M R Lee, P H Whiting |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 101
Issue 2
Pg. 301-6
(Oct 1990)
ISSN: 0007-1188 [Print] England |
PMID | 2124159
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- gamma-glutamyl DOPA
- Dihydroxyphenylalanine
- Glycerol
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Topics |
- Acute Kidney Injury
(chemically induced, metabolism)
- Animals
- Dihydroxyphenylalanine
(analogs & derivatives, pharmacokinetics)
- Glycerol
- Kidney Diseases
(metabolism)
- Male
- Nephrectomy
- Rats
- Rats, Inbred Strains
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