- Metabolism: After oral administration L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora. Major metabolites include trimethylamine N-oxide and [3H]-gamma-butyrobetaine. Route of Elimination: Following a single intravenous dose, 73.1 +/- 16% of the dose was excreted in the urine during the 0-24 hour interval. Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 days. Half Life: 17.4 hours (elimination) following a single intravenous dose.
- Uses/Sources: For treatment of primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency. Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease.
- Symptoms: Adverse effects include hypertension, fever, tachycardia and seizures.
- Route of Exposure: Intravenous, Oral. Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD<sub>50</sub> > 8g/kg (mouse, oral).
Mechanism of Action
|Target Name||Mechanism of Action||References|
Liver carboxylesterase 1
Solute carrier family 22 member 16
Carnitine O-palmitoyltransferase 1, liver isoform
Solute carrier family 22 member 4
Solute carrier family 22 member 5
Mitochondrial carnitine/acylcarnitine carrier protein CACL
Mitochondrial carnitine/acylcarnitine carrier protein
Peroxisomal carnitine O-octanoyltransferase
Carnitine O-palmitoyltransferase 2, mitochondrial
|Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.||