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 met abolism. Secondary carnitine deficiency may develop in patients with end-st age renal disease undergoing long-term hemodialysis because of dialytic los s. In these patients L-carnitine can be administered to restore plasma and tissue levels. The objective of this study was to evaluate the pharmacokine tics of intravenous L-carnitine in patients undergoing long-term hemodialys is. Methods: Twelve patients undergoing three dialysis sessions/week received L -carnitine intravenously (20 mg . kg(-1)) at the end of each dialysis sessi on for 9 weeks. Plasma samples were analyzed for L-carnitine, acetyl-L-carn itine, and total carnitine by HPLC. Results: Under baseline conditions, the mean +/- SD predialysis plasma conc entration of L-carnitine was 19.5 +/- 5.6 mu mol/L, decreasing to 5.6 +/- 1 .9 mu mol/L at the end of the dialysis session. These concentrations were s ubstantially lower than endogenous levels in healthy human beings. Under ba seline conditions the extraction ratios of L-carnitine and acetyl-L-carniti ne by the dialyser were 0.74 +/- 0.07 and 0.71 +/- 0.11, respectively. Duri ng repeated dosing, there was accumulation of L-carnitine in plasma, and af ter 9 weeks of dosing, the predialysis and postdialysis plasma levels were 191 +/- 54.1 and 41.8 +/- 13.0 mu 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 hemodialy sis is extremely efficient and that patients undergoing hemodialysis had pl asma concentrations that were substantially lower than normal, particularly during dialysis. During repeated administration of L-carnitine, the predia lysis and post-dialysis 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 ti ssue pool that includes skeletal muscle.