Disposition and metabolite kinetics of oral L-carnitine in humans

J Clin Pharmacol. 2006 Oct;46(10):1163-70. doi: 10.1177/0091270006292851.

Abstract

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 microM to 80.5 +/- 12.5 microM 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 microM), 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.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Carnitine / administration & dosage
  • Carnitine / metabolism
  • Carnitine / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Humans
  • Kidney / metabolism
  • Male
  • Metabolic Clearance Rate
  • Methylamines / blood
  • Methylamines / metabolism
  • Nausea / chemically induced
  • Taste Disorders / chemically induced
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / adverse effects
  • Vitamin B Complex / pharmacokinetics*

Substances

  • Methylamines
  • Vitamin B Complex
  • trimethyloxamine
  • trimethylamine
  • Carnitine