L-カルニチン

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

195-198

197 °C (dec)

132.9 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]

130 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine]

133.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

132.9 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

This chemical does not meet GHS hazard criteria for 10.5% (159 of 1511) of reports.

Warning

H315 (89.5%): Causes skin irritation [Warning Skin corrosion/irritation]

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364 (click each P-code to see the statement)

Aggregated GHS information provided per 1511 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: 1-Propanaminium, 3-carboxy-2-hydroxy-N,N,N-trimethyl-, inner salt, (2R)-

Regulation (EC) No 1831/2003 (amended)

Status: Active Update: 04-05-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/30871

Carnitine: Does not have an individual approval but may be used under an appropriate group standard

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levocarnitine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

... The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-mL solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 mL of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.

... The effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of L-carnitine (LC) and its main ester, acetyl-L-carnitine (ALC), in cancer patients /was examined/. ... Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.

... The rats were divided into four groups: group 1, control (0.9% NaCl); group 2, doxorubicin (DOX) injection (7.5 mg/kg, i.v.); group 3, DOX plus low dose (40 mg/kg) L-carnitine; and group 4, DOX plus high dose (200 mg/kg) L-carnitine. L-carnitine was administered 1 h before doxorubicin injection and daily thereafter for 15 days. ... Rats in group 2 were associated with hypoalbuminemia, hyperlipidemia, high urinary excretion of protein and elevated plasma creatinine and urea nitrogen. The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) decreased with increased renal vascular resistance (RVR). Kidney catalase (CAT) activity was decreased. In group 3 and 4, plasma triglyceride and cholesterol declined. L-carnitine improved renal functions by elevated GFR and ERPF and decreased plasma creatinine and urea nitrogen. The kidney CAT activity were increased significantly compared with group 2. From histopathological results, group 2 rats were found to have glomerular capillary dilation and tubular dilation. The lesions were less in group 3 and 4 rats...

... Recent literature documents no cases of allergic reactions or serious side effects associated with the administration of carnitine when given patients with acute ingestions of valproic acid. Other findings suggest that carnitine increases the survival rate of patients who develop valproic-acid-induced hepatotoxicity. Early intervention with iv rather than enteral L-carnitine was associated with the greatest hepatic survival. Isolated pediatric case reports show that carnitine administration may reverse toxic metabolic pathways but may not hasten clinical improvement. .../Carnitine/

For more Interactions (Complete) data for L-CARNITINE (17 total), please visit the HSDB record page.

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.

L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. ... In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate.

/SIGNS AND SYMPTOMS/ At doses of approximately 3 grams/day, carnitine supplements may cause nausea, vomiting, abdominal cramps, diarrhea, and a "fishy" body odor. More rare side effects include muscle weakness in uremic patients and seizures in those with seizure disorders. /Carnitine/

/SIGNS AND SYMPTOMS/ Mild myasthenia has been reported in uremic patients taking the racemic mixture D,L-carnitine. /D,L-carnitine/

/ALTERNATIVE and IN VITRO TESTS/ In Hela cells, L-carnitine reduced glucocorticoid receptor-alpha affinity for its steroid ligand, and triggered nuclear translocation of the receptor. It suppressed glucocorticoid receptor-mediated tumor necrosis factor-alpha and interleukin-12 release by human primary monocytes stimulated with lipopolysaccharide ex vivo. All the these effects of L-carnitine were concentration dependent.

/ALTERNATIVE and IN VITRO TESTS/ ... Whether addition of L-carnitine altered the tumor cytotoxic effects of epirubicin /was determined/ using a number of in vitro cell viability assays in different breast cancer cell lines including BT549, MDA-MB-435, NCI-ADR-RES, MCF7 and T47D. Additionally ... the ability of cells to respond to L-carnitine following analysis of the expression of carnitine metabolic enzymes by RT-PCR /was investigated/. ... Supplementation with L-carnitine had no effect on the ability of epirubicin to kill a variety of breast cancer cell lines. Additionally, no differences in the induction of apoptosis by epirubicin were observed. Furthermore, all cell lines examined expressed proteins required for carnitine uptake and use. ... These results suggest that supplementation with L-carnitine in patients undergoing epirubicin treatment could be safely used to reduce associated cardiotoxicities without fear that the efficacy of chemotherapy is jeopardized.

For more Human Toxicity Excerpts (Complete) data for L-CARNITINE (6 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Levocarnitine

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Normotensive, Wistar-Kyoto rats.... (n = 20) were orally administered 0.2 g carnitine/kg body weight per day for a total period of 8 weeks. Kinetic parameters of L-carnitine uptake were calculated by non-linear regression, and the relative abundance of the carnitine transporter, OCTN2, was determined by Western blot analysis. ... Initial rates and maximal overshoot levels of Na+-dependent L-carnitine transport were significantly reduced in BBMVs from L-carnitine-treated rats compared with untreated animals. Similarly, the maximal transport rate (Vmax) of OCTN2 was lower in treated rats. However, no differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. The amount of OCTN2 protein was also decreased in L-carnitine-fed rats, this reduction being similar to that of the Vmax. These results were accompanied by an increase in the serum levels and also in the renal excretion of both free and esterified carnitine in treated rats, indicating that the long-term administration of L-carnitine leads to increased renal carnitine clearance. ... These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human doses used for the treatment of primary and secondary L-carnitine deficiency on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to L-carnitine.

/ALTERNATIVE and IN VITRO TESTS/ ... Calf lens tissue was incubated with both L-carnitine and acetyl-L-cartinine (ALC) for 15 days. The results showed that while L-carnitine had no effect on in vitro glycation, acetyl-L-carnitine decreased crystallin glycation by 42 percent.

/GENOTOXICITY/ Mutagenicity data indicate no mutagenicity ...

Precautions: ... There are no adequate and well-controlled studies in pregnant women ... Supplemental L-carnitine should be used by pregnant women only if clearly indicated and only under medical supervision. It is not known whether L-carnitine is excreted in human milk. Supplemental L-carnitine is not advised for nursing mothers.Those with seizure disorders should only used L-carnitine under medical advisement and supervision.

While data specific to L-carnitine were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Treatment of overdose: To enhance elimination: Removing levocarnitine from plasma via hemodialysis. Supportive care: Treatment is symptomatic and supportive.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levocarnitine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".

A16AA01

A - Alimentary tract and metabolism

QA - Alimentary tract and metabolism

L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.

L-Carnitine and extramitochondrial carnitine palmitoyltransferase (CPT, /catalyzing transesterification between coenzyme A and L-carnitine/) are important modulators of long-chain fatty acid utilization for membrane phospholipid biosynthesis and remodeling. L-Carnitine acts as a reservoir of long-chain fatty acids for incorporation into erythrocyte membrane phospholipids during repair after oxidative insults, and for use in the synthesis of dipalmitoylphosphatidylcholine, the major component of surfactant, in lung alveolar cells.

Although L-carnitine is supplied exogenously as a component of the diet and can also be synthesized endogenously, evidence suggests both primary and secondary deficiencies do occur. Carnitine deficiency can be acquired or a result of inborn errors of metabolism. Pre-term infants are at risk for developing a carnitine deficiency due to impaired synthesis and insufficient renal tubular resorption. Deficiency can result in cardiomyopathy, congestive heart failure, encephalopathy, hepatomegaly, impaired growth and development in infants, and neuromuscular disorders. Primary carnitine deficiency, although rare, is characterized by low plasma, red blood cell, and tissue levels of carnitine, and generally presents with symptoms such as muscle fatigue, cramps, and myoglobinemia following exercise. Additional symptoms of chronic carnitine deficiency can include hypoglycemia, progressive myasthenia, hypotonia, or lethargy. Secondary carnitine deficiency is not as rare and is most commonly associated with dialysis in chronic renal failure, although it can also be induced by intestinal resection, severe infection, and liver disease. Other conditions associated with a carnitine deficiency include cancer, diabetes, Alzheimer's disease, and heart failure. Pathological manifestations of chronic deficiency include accumulation of neutral lipid within skeletal muscle, cardiac muscle, and liver; a disruption of muscle fibers; and an accumulation of large aggregates of mitochondria within skeletal and smooth muscle.

HIV-infected individuals often accumulate fat in some areas of the body and lose fat in others and develop high levels of blood fats (hyperlipidemia) and insulin resistance, which together constitute the lipodystrophy syndrome. This syndrome may represent mitochondrial toxicity brought about by the HIV infection and the antiretroviral drugs used to treat it, and can induce a carnitine deficiency that limits mitochondrial fat metabolism. /Carnitine/

For more Bionecessity (Complete) data for L-CARNITINE (16 total), please visit the HSDB record page.

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 &micro;mol/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.

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.

L-Carnitine is a peripheral antagonist of thyroid hormone action in some tissues. It inhibits thyroid hormone entry into cell nuclei. In a controlled clinical trial, L-carnitine was shown to reverse or prevent some symptoms of hyperthyroidism.

... Mortality and metabolic consequences of acute ammonium intoxication in mice are reduced by pharmacologic admin of L-carnitine. The mechanism for this effect may have 2 components. L-Carnitine admin normalizes the redox state of the brain (perhaps by incr the avail of beta-hydroxybutyrate and/or acetyl-L-carnitine to the brain), and it incr the rate of urea synth in the liver, perhaps in part by activation of the glucocorticoid receptor. At least part of the protective effect is associated with flux through the carnitine acyltransferases, as analogs of L-carnitine that are competitive inhibitors of carnitine acyltransferases enhance the toxicity of acute ammonium admin. Thus, it has been proposed that L-carnitine incr urea synth in the liver by facilitating fatty acid entry into mitochondria, leading to incr flux through the beta-oxidation pathway, an incr of intramitochondrial reducing equivalents, and enhancement of ATP production. ...

Levocarnitine is necessary for normal mammalian fat utilization and energy metabolism. It facilitates entry of long-chain fatty acids into cellular mitochondria, where they are used during oxidation and energy production. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations.

Carnitine's primary mechanism of action is apparently attributable to its role as a cofactor in the transformation of free long-chain fatty acids into acylcarnitines for subsequent transport into the mitochondrial matrix. Carnitine is involved in the metabolism of ketones for energy and the conversion of branched-chain amino acids - valine, leucine, and isoleucine - into energy. /Carnitine/

L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.

17.4 hours (elimination) following a single intravenous dose.

Distribution: 0.585 hours; Elimination: 17.4 hours

... Half-life /in blood/ ca 15 hr ...

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.

In mammals, L-carnitine is synthesized from epsilon-N-trimethyllysine, which is derived from post-translationally methylated lysine residues in proteins, and protein turnover. In normal humans, the rate of synth is est to be ca 1.2 umol/kg/day. The rate of L-carnitine biosynth is regulated by the avail of epsilon-N-trimethyllysine. Thus, conditions that incr protein methylation and/or protein turnover may incr the rate of L-carnitine biosynth.

Synthesis of carnitine begins with methylation of the amino acid L-lysine by S-adenosylmethionine (SAMe). Magnesium, vitamin C, iron, vitamins B3 and B6, and alpha-ketoglutarate - along with the cofactors responsible for creating SAMe (methionine, folic acid, vitamin B12, and betaine) - are all required for endogenous carnitine synthesis.

Unabsorbed L-carnitine is degraded by micro-organisms in the large intestine. Major metabolites identified are trimethylamine oxide in urine and gamma-butyrobetaine in feces.

Carnitine plays an indispensable role in fatty acid oxidation. Previous studies revealed that fetal carnitine is derived from the mother via transplacental transfer. Recent studies demonstrated the presence and importance of an active fatty acid oxidation system in the human placenta and in the human fetus. In view of these findings ... carnitine metabolism /was studied/ in the fetal-placental unit by measuring carnitine metabolites, intermediary metabolites of carnitine biosynthesis, as well as the activity of carnitine biosynthesis enzymes in human term placenta, cord blood and selected embryonic and fetal tissues (5-20 weeks of development). Placenta contained low but detectable activity of gamma-butyrobetaine dioxygenase. This enzyme, which was considered to be expressed only in kidney, liver and brain, catalyzes the last step in the carnitine biosynthesis pathway. In addition, ... human fetal kidney, liver and spinal cord already have the capacity to synthesize carnitine. The ability of the placenta and fetus to synthesize carnitine suggests that in circumstances when maternal carnitine supply is limited, carnitine biosynthesis by the fetal-placental unit may supply sufficient carnitine for placental and fetal metabolism. /Carnitine/

For more Metabolism/Metabolites (Complete) data for L-CARNITINE (7 total), please visit the HSDB record page.

0G389FZZ9M

LEVOCARNITINE

Chemical Structure [CS] - Carnitine

Established Pharmacologic Class [EPC] - Carnitine Analog

Levocarnitine is a Carnitine Analog.

LEVOCARNITINE

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

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.

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.

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

L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for beta-oxidation. ... In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1-6 g, the absolute bioavailability is 5-18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet. L-Carnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After iv administration, the initial distribution volume of L-carnitine is typically about 0.2-0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle. L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1-3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98-99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40-60 umol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high iv doses. ...

In mammals, the carnitine pool consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary L-carnitine is 54-87% and is dependent on the amount of L-carnitine in the meal. Absorption of L-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose. Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues). At normal dietary L-carnitine intake, whole-body turnover time in humans is 38-119 hr. In vitro experiments suggest that acetyl-L-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-L-carnitine concentration was increased 43% after oral acetyl-L-carnitine supplements of 2 g/day, indicating that acetyl-L-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-L-carnitine is rapidly, but not completely hydrolyzed, and acetyl-L-carnitine and L-carnitine concentrations return to baseline within 12 h. At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating L-carnitine concentration increases (as after high-dose intravenous or oral administration of L-carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating L-carnitine concentration to baseline. Elimination kinetics for acetyl-L-carnitine are similar to those for L-carnitine. There is evidence for renal tubular secretion of both L-carnitine and acetyl-L-carnitine. ...

An essential cofactor in fatty acid metabolism; Highest concentrations in red meat, dairy, beans, and avocado; Used as a vitamin; [Merck Index]

Used to treat carnitine deficiency

Used therapeutically for myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism

Use (kg; approx.) in Germany (2009): >1000

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.

Levocarnitine oral solution USP: 100 mg/mL (Carnitor). Levocarnitine tablets USP: 330 mg (Carnitor). Levocarnitine injection: 200 mg/mL (Carnitor).

L-carnitine is avail in a few forms: oral L-carnitine ... iv L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine. The avail salts ... are L-carnitine HCL, L-carnitine tartrate and L-carnitine fumarate ... /Supplied in/ capsules, injection, liquid, solution, tablets, wafer

Trade names: Carnitor ... Carnitine-300 ... Carni Fuel ... Mega L-Carnitine ... Maximal Burner Carnitine ... Proxeed ...