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|Title:||Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis|
|Citation:||Clinical Pharmacology & Therapeutics, 2000; 68(3):238-249|
|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.|
|Appears in Collections:||Medicine publications|
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