(-)-Carnitine

161.199

161.105194

208-768-0

0G389FZZ9M

759132|741806

DTXSID4023208

C26657

White, crystalline, hygroscopic powder

A16AA01|A - Alimentary tract and metabolism

29239000

60.36000

-0.2

Solid

0.64 g/cm3

196-198 °C

-32 ° (C=1, H2O)

2500 g/L (20 ºC)

2-8°C

LD50 orally in Rabbit: > 5000 mg/kg

The specific optical rotation is between -29 and -32

3.8None

133.1 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|130 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]|132.9 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|132.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 2.7X10-11 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

3

R36/37/38:Irritating to eyes, respiratory system and skin .

S26-S36-S37/39

BP2980000

Xi

Hygroscopic

P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, P362

H315

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 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".

Thorne Research, Inc.; Monograph on L-Carnitine; Alternative Medicine Review 10(1) (2005). Available from: http://www.thorne.com/altmedrev/.fulltext/10/1/42.pdf as of February 25, 2008.

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P264, P280, P302+P352, P305+P351+P338, P321, P332+P313, P337+P313, and P362|Aggregated GHS information provided by 1541 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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

... 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.

LD50 Rat iv 5.4 g/kg|LD50 Mouse oral 19.2 g/kg

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.

None

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.

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).

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 is indicated 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. /Included in US product labeling/|Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease supported on hemodialysis. /Included in US product labeling/|Levocarnitine oral solution is used for the prevention and treatment of carnitine deficiency secondary to valproic acid toxicity. /NOT included in US product labeling/|L-Carnitine, acetyl-L-carnitine, and/or propionyl-L-carnitine may be used for replacement therapy to restore normal carnitine concn and/or a normal nonesterified-to-esterified carnitine ratio ... For primary and some secondary carnitine deficiencies ... L-carnitine is used for replacement therapy.|For more Therapeutic Uses (Complete) data for L-CARNITINE (29 total), please visit the HSDB record page.

Various mild gastrointestinal complaints have been reported during the long-term administration of oral L- or D,L-carnitine; these include transient nausea and vomiting, abdominal cramps, and diarrhea. Mild myasthenia has been described only in uremic patients receiving D,L-carnitine. Gastrointestinal adverse reactions with carnitor (levocarnitine) Oral Solution or carnitor SF (levocarnitine) Sugar-Free Oral Solution dissolved in liquids might be avoided by a slow consumption of the solution or by a greater dilution. Decreasing the dosage often diminishes or eliminates drug-related patient body odor or gastrointestinal symptoms when present. Tolerance should be monitored very closely during the first week of administration, and after any dosage increases. Seizures have been reported to occur in patients with or without pre-existing seizure activity receiving either oral or intravenous levocarnitine. In patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported.|... Oral L-carnitine at a dose of 1 g daily was administered for twelve days to six patients with end-stage renal disease undergoing hemodialysis thrice weekly. Pre-dialysis plasma concentrations of L-carnitine (mean +/- SD) increased significantly (P < 0.05) from day 1 (baseline; 32.4 +/- 6.1 uM) to day 8 (66.1 +/- 13.8 uM) remaining constant thereafter. Although plasma levels of trimethylamine remained unaltered, the pre-dialysis plasma concentrations of trimethylamine-N-oxide increased significantly (P < 0.05) from day 1 (289.1 +/- 236.1 microM) to day 12 (529.0 +/- 237.9 uM). The hemodialysis clearances for L-carnitine, trimethylamine and trimethylamine-N-oxide were 14.3 +/- 8.2, 14.1 +/- 10.6 and 12.4 +/- 5.4 L/h, respectively, indicating their efficient removal by dialysis. Oral administration of L-carnitine at a dose of 1 g daily increases plasma concentrations of this substance to physiological levels in patients with end-stage renal disease who are undergoing hemodialysis. However, concerns about the possible deleterious consequences of such a dosage regimen still remain given that plasma concentrations of trimethylamine-N-oxide were continually rising and approximately doubled in a two-week period.|... Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some drug-induced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser ...|The aim of our work was to test the influence of L-carnitine supplementation on secondary hyperparathyroidism and bone metabolism in hemodialyzed patients in a randomized study. Eighty-three chronically hemodialyzed patients were observed; 44 were supplemented with L-carnitine (15 mg/kg iv after each hemodialysis for 6 months), while 39 took placebo. Levels of free carnitine (CAR), calcium (Ca), inorganic phosphate (P), Ca x P product, parathormone (PTH), bone-specific alkaline phosphatase (b-ALP), osteocalcin (OC), and osteoprotegerin (OPG) were monitored. In comparison with pretreatment values, changes of some selected parameters occurred in the supplemented patients after 6 months (data are expressed as medians; NS, nonsignificant change): PTH, 186.0 vs. 135.5 ng/L (NS); b-ALP, 13.9 vs. 13.2 ug/L (P < 0.05); OC, 78.3 vs. 68.8 ug/L (NS); OPG, 144.0 vs. 182.0 ng/L (P < 0.05). In the controls, there were the following changes: PTH, 148.0 vs. 207.0 ng/L (NS); b-ALP, 15.2 vs. 13.2 ug/L (P < 0.05); OC, 62.7 vs. 79.8 ug/L (P < 0.05); OPG, 140.0 vs. 164.0 ng/L (NS). A significant correlation was found between CAR and OPG changes (r = 0.51, P < 0.001) in the supplemented patients. The supplementation led to a significant increase of serum OPG concentration. Nevertheless, ...only nonsignificant tendencies to correction of secondary hyperparathyroidism and reduction of bone turnover in hemodialyzed patients supplemented with L-carnitine /were observed/ in contrast to controls. At this point, the use of L-carnitine does not seem to be justified.|For more Drug Warnings (Complete) data for L-CARNITINE (9 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 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.

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. ...|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 < 0.05) from a baseline of 54.2 +/- 9.3 uM to 80.5 +/- 12.5 uM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P <0.001) 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 uM), and its renal clearance decreased with increasing dose (P <0.05). 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.|Evidence indicates L-carnitine is absorbed in the intestine by a combination of active transport and passive diffusion. Reports of bioavailability following an oral dose have varied substantially, with estimates as low as 16 to 18% and as high as 54 to 87% ... The mucosal absorption of carnitine appears to be saturated at about a 2-g dose. Max blood concn is reached approx 3.5 hr after an oral dose and slowly decr, with a half-life of about 15 hr. Elimination of carnitine occurs primarily through the kidneys. The heart, skeletal muscle, liver, kidneys, and epididymis have specific transport systems for carnitine that concentrate carnitine within these tissues. Despite evidence indicating incr levels of free carnitine and carnitine metabolites in the blood and urine following an oral dose, no significant change in RBC carnitine levels was noted in healthy subjects, suggesting either a slow repletion of tissue stores of carnitine following an oral dose or a low capability to transport carnitine into tissues under normal conditions.|For more Absorption, Distribution and Excretion (Complete) data for L-CARNITINE (11 total), please visit the HSDB record page.

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.

17.4 hours (elimination) following a single intravenous dose.|Distribution: 0.585 hours; Elimination: 17.4 hours|... Half-life /in blood/ ca 15 hr ...

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.

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/

/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.

Bicarnesine

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 ...

Analyte: levocarnitine; matrix: bulk material; procedure: high-performance liquid chromatography with fluorescence detection at 485 nm (excitation) and 540 nm (emission); limit of detection: 100 fmole|Analyte: levocarnitine; matrix: pharmaceutical preparation (tablet); procedure: high-performance liquid chromatography with fluorescence detection at 365 nm (excitation) and 412 nm (emission) or ultraviolet detection at 250 nm; limit of detection: 1 pg|Analyte: levocarnitine; matrix: pharmaceutical preparation (tablet); procedure: high-performance liquid chromatography with fluorescence detection at 355 nm (excitation) and 420 nm (emission); limit of detection: 500 ng/mL|Analyte: levocarnitine; matrix: pharmaceutical preparation (injection solution, syrup, tablet); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of detection: 50 ug/mL|For more Analytic Laboratory Methods (Complete) data for L-CARNITINE (6 total), please visit the HSDB record page.

Analyte: levocarnitine; matrix: blood (plasma); procedure: capillary electrophoresis with ultraviolet detection at 214 nm; limit of detection: 20 uM|Analyte: levocarnitine; matrix: blood (plasma); procedure: capillary electrophoresis with fluorescence detection at 320 nm (excitation) and 405 nm (emission); limit of detection: <1 uM|Analyte: levocarnitine; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 340 nm (excitation) and 475 nm (emission); limit of detection: 240 nM|Analyte: levocarnitine; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 248 nm (excitation) and 418 nm (emission); limit of detection: 5 uM|For more Clinical Laboratory Methods (Complete) data for L-CARNITINE (11 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Cosmetics -> Cleansing; Foam boosting