L-Carnitine

Synonyms :
(-)-Carnitine, (-)-L-Carnitin, (-)-L-Carnitine, (R)-Carnitine, (S)-Carnitine, 3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium, 3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium hydroxide, inner salt, Carnicor, Carnitene, Carnitine, Carnitor, Karnitin, L-Carnitine, Levocarnitin, Levocarnitina, Lévocarnitine, Levocarnitinum, Vitamin bt

Status : approved

Category

Vitamin B Complex

Description

Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [PubChem]

Used

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.

Mechanism Of Action

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.

Dosage

Form Route Strength
Injection, solution intravenous 1 g/5mL
Solution intravenous 200 mg
Liquid oral 100 mg
Injection intravenous 1 g/5mL
Injection intravenous 2.5 g/12.5mL
Injection, solution intravenous 200 mg/mL
Solution oral 1 g/10mL
Tablet oral 330 mg

Pharmacodynamics

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. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The “vitamin BT” form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

Toxic Effect

LD50 > 8g/kg (mouse, oral). Adverse effects include hypertension, fever, tachycardia and seizures.

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.

Absorption

Absolute bioavailability is 15% (tablets or solution). Time to maximum plasma concentration was found to be 3.3 hours.

Half Life

17.4 hours (elimination) following a single intravenous dose.

Protein Binding

None

Elimination Route

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.

Clearance

Total body clearance was found to be a mean of 4L/h.

Volume of Distribution

The steady state volume of distribution (Vss) of an intravenously administered dose, above endogenous baseline levels, was calculated to be 29.0 +/- 7.1L. However this value is predicted to be an underestimate of the true Vss.

Chemical Classification

This compound belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.

Hydroxy fatty acids

Organic compounds

Lipids and lipid-like molecules

Fatty Acyls

Fatty acids and conjugates

Salt : L-Carnitin Hydrochloride

Chemical Name

(-)-Carnitine

Brands

name Dosage form Country
Carnitor tablet US
Carnitor solution US
Carnitor injection, solution US
Carnitor – Liq IV 200mg/ml solution Canada
Carnitor – Liq Orl 100mg/ml liquid Canada
Carnitor -tab 330mg tablet Canada
Carnitor Sf solution US
Levocarnitine injection US
Levocarnitine injection US
Levocarnitine solution US
Levocarnitine solution US
Levocarnitine solution US
Levocarnitine tablet US
Levocarnitine tablet US
Levocarnitine solution US
Levocarnitine injection, solution US

Drug Drug Interactions

  •  Acenocoumarol  : May enhance the anticoagulant effect of Vitamin K Antagonists.
  •  Warfarin  : May enhance the anticoagulant effect of Vitamin K Antagonists.

Calculated Property

kind Value Source
logP -2.9 ALOGPS
logS -1.6 ALOGPS
Water Solubility 5.33e+00 g/l ALOGPS
logP -4.9 ChemAxon
IUPAC Name (3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate ChemAxon
Traditional IUPAC Name L-carnitine ChemAxon
Molecular Weight 161.1989 ChemAxon
Monoisotopic Weight 161.105193351 ChemAxon
SMILES C[N+](C)(C)C[C@H](O)CC([O-])=O ChemAxon
Molecular Formula C7H15NO3 ChemAxon
InChI InChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3/t6-/m1/s1 ChemAxon
InChIKey InChIKey=PHIQHXFUZVPYII-ZCFIWIBFSA-N ChemAxon
Polar Surface Area (PSA) 60.36 ChemAxon
Refractivity 63.49 ChemAxon
Polarizability 16.93 ChemAxon
Rotatable Bond Count 4 ChemAxon
H Bond Acceptor Count 3 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 4.2 ChemAxon
pKa (strongest basic) -3.6 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 0 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Solute carrier family 22 member 4 : in Human
  • Solute carrier family 22 member 5 : in Human
  • Carnitine O-acetyltransferase : in Human
  • Mitochondrial carnitine/acylcarnitine carrier protein CACL : in Human
  • Mitochondrial carnitine/acylcarnitine carrier protein : in Human
  • Peroxisomal carnitine O-octanoyltransferase : in Human
  • Carnitine O-palmitoyltransferase 2, mitochondrial : in Human
  • Carnitine O-palmitoyltransferase 1, liver isoform : in Human
  • Xanthine dehydrogenase/oxidase : in Human
  • Liver carboxylesterase 1 : in Human
  • Myeloperoxidase : in Human