Pharmacokinetics of ?-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis

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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 μmol/L, decreasing to 5.6 ± 1.9 μmol/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 μmol/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. Clinical Pharmacology & Therapeutics (2000) 68, 238–249; doi: 10.1067/mcp.2000.108850

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