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 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.
Bain
Marcus A
MA
Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Milne
Robert W
RW
Evans
Allan M
AM
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002331:Carnitine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008744:Methylamines / Q000097:blood / Q000378:metabolism; D009325:Nausea / Q000139:chemically induced; D013651:Taste Disorders / Q000139:chemically induced; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D008744:Methylamines; D014803:Vitamin B Complex; C005855:trimethyloxamine; C023336:trimethylamine; D002331:Carnitine