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Title: The influence of experimental renal failure on the pharmacokinetics of drugs : a study of warfarin and gamma-glutamyl-L-dopa
Author: Boateng, Yaw Ababio
ISNI:       0000 0001 3468 6854
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1990
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The influence of experimental renal failure on the pharmacokinetics of drugs has been studied using warfarin and gamma-glutamyl-l-dopa (gludopa) as model drugs. The pharmacokinetics of gludopa in normal rats and normal human volunteers have also been studied. The pharmacokinetics of warfarin were unaltered by glycerol-induced acute renal failure (ARF) and 5/6 nephrectomy-induced chronic renal failure (CRF). Using the isolated perfused rat liver technique the hepatic uptake of warfarin was unaltered in experimental renal failure. The pharmacokinetics of gludopa was linear across the dose range 2 to 7.5 in normal rats. The total body clearance was rapid. Gludopa had a short half-life and a large apparent volume of distribution. The fraction of gludopa metabolised to L-dopa was 0.54. About 10% of an injected dose was excreted unchanged. ARF had no effect on the kinetics of gludopa in rats. In functionally nephrectomised (anephric) rats about 70% of the elimination of gludopa was attributable to the kidneys. In normal human volunteers the kinetics of gludopa were linear in the dose range 100 μ^-1 to 250 μ The clearance was rapid. Less than 1% of an injected dose was excreted unchanged by the kidneys. Urinary dopamine concentrations were greatest 30 minutes after a bolus dose of gludopa reaching 215 and 61 times baseline values for a gludopa dose of 250 μ^-1 and 100 μ respectively. These results suggest that the kinetics of warfarin and gludopa remain unaltered in experimental renal failure. Gludopa is an efficient pro-drug for L-dopa and dopamine. The kidney is the major site for gludopa metabolism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry