Disposition and Metabolite Kinetics of Oral L‐carnitine in Humans

The pharmacokinetics of L‐carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L‐carnitine across an 8‐hour dose interval increased significantly (P <.05) from a baseline of 54.2 ± 9.3 μM to 80.5 ± 12.5 μM following the 0.5‐g dose; there was no further increase at higher doses. There was a significant increase (P <.001) in the renal clearance of L‐carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L‐carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine‐N‐oxide from baseline was evident only for the 2‐g dose of L‐carnitine (from 34.5 ± 2.0 to 149 ± 145 μM), and its renal clearance decreased with increasing dose (P <.05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine‐N‐oxide. In conclusion, the pharmacokinetics of oral L‐carnitine display nonlinearity above a dose of 0.5 g 3 times a day.