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https://hdl.handle.net/2440/9380
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Type: | Journal article |
Title: | Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis |
Author: | Evans, A. Faull, R. Fornasini, G. Lemanowicz, E. Longo, A. Pace, S. Nation, R. |
Citation: | Clinical Pharmacology and Therapeutics, 2000; 68(3):238-249 |
Publisher: | Mosby Inc |
Issue Date: | 2000 |
ISSN: | 0009-9236 1532-6535 |
Statement of Responsibility: | Allan M. Evans, Randall Faull, Gianfranco Fornasini, Edward F. Lemanowicz, Antonio Longo, Silvia Pace, and Roger L. Nation |
Abstract: | OBJECTIVE: L-Carnitine is an endogenous molecule involved in fatty acid metabolism. Secondary carnitine deficiency may develop in patients with end-stage renal disease undergoing long-term hemodialysis because of dialytic loss. In these patients L-carnitine can be administered to restore plasma and tissue levels. The objective of this study was to evaluate the pharmacokinetics of intravenous L-carnitine in patients undergoing long-term hemodialysis. METHODS: Twelve patients undergoing three dialysis sessions/week received L-carnitine intravenously (20 mg kg-1) at the end of each dialysis session for 9 weeks. Plasma samples were analyzed for L-carnitine, acetyl-L-carnitine, and total carnitine by HPLC. RESULTS: Under baseline conditions, the mean SD predialysis plasma concentration of L-carnitine was 19.5 5.6 mol/L, decreasing to 5.6 1.9 mol/L at the end of the dialysis session. These concentrations were substantially lower than endogenous levels in healthy human beings. Under baseline conditions the extraction ratios of L-carnitine and acetyl-L-carnitine by the dialyser were 0.74 0.07 and 0.71 0.11, respectively. During repeated dosing, there was accumulation of L-carnitine in plasma, and after 9 weeks of dosing, the predialysis and postdialysis plasma levels were 191 54.1 and 41.8 13.0 mol/L, respectively. The predialysis and postdialysis plasma levels of L-carnitine decreased once dosing was ceased but had not returned to pretreatment levels after 6 weeks. CONCLUSION: The study demonstrated that removal of L-carnitine by hemodialysis is extremely efficient and that patients undergoing hemodialysis had plasma concentrations that were substantially lower than normal, particularly during dialysis. During repeated administration of L-carnitine, the predialysis and postdialysis concentrations of the compound increased steadily, reaching an apparent steady state after about 8 weeks. It is proposed that this accumulation arose from the distribution of l-carnitine into a deep tissue pool that includes skeletal muscle. |
Keywords: | Humans Kidney Failure, Chronic Carnitine Acetylcarnitine Renal Dialysis Chromatography, High Pressure Liquid Injections, Intravenous Analysis of Variance Area Under Curve Longitudinal Studies Half-Life Adult Aged Middle Aged Female Male |
Rights: | Copyright © 2000 by Mosby, Inc. |
DOI: | 10.1067/mcp.2000.108850 |
Published version: | http://dx.doi.org/10.1067/mcp.2000.108850 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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