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

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 became 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 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 staples 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 actuation of L-carnitine 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 study 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.