Multiple‐Dose Pharmacokinetics and Bioequivalence L-Carnitine 330-mg Tablet versus 1-g Chewable Tablet versus Enteral Solution in Healthy Adult Male Volunteers

Sahajwalla, Chandrahas; Helton, Edward D.; Purich, Edward D.; Hoppel, Charles L.; Cabana, Bernard E.

doi:10.1002/jps.2600840520

Cited by 39 publications

(33 citation statements)

References 11 publications

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“…17,18 In humans, the time to achieve maximum plasma concentrations after oral administration of L-carnitine can be up to 4-6 hours. 19 In this study we found that the absorption half-life of L-carnitine was about 1. (Fig 1A), ALC ( Fig 1B) and PLC (Fig 1C) after single oral administration.…”

Section: Discussionmentioning

confidence: 65%

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Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Cao¹,

Wang²,

Liu³

et al. 2009

CIM

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Clin Invest Med 2009; 32 (1): E13-E19. AbstractPurpose: To investigate the pharmacokinetics of Lcarnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl -L-carnitine (PLC) in healthy volunteers after single L-carnitine administration. Methods: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC. Results:The maximum plasma concentration (Cmax) and area under the curve (AUC0-) of L-carnitine was 84.7±25.2 μmol·L -1 ·h and 2676.4±708.3 μmol·L -1 ·h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3±15.0 and 3.4±0.46 h, respectively. The Cmax of ALC (12.9±5.5 μmol·L -1 ) and PLC (5.08±3.08 μmol·L -1 ) was lower than Lcarnitine (P<0.01), so as the AUC0-(166.2±77.4 and 155.6±264.2μmol·L -1 ·h, respectively, P<0.01). The half-life of ALC (35.9±28.9h) and PLC (25.7±30.3 h) was also shorter than L-carnitine (P<0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5±161.7, 368.3±134.8 and 61.3±37.8μmol, respectively. Conclusion: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC.L-carnitine (3-hydroxy-4-N-trimethylammonium butyrate) is an endogenous compound mainly derived from food stuff, such as meat and dairy products. [1][2][3] It is also synthesized in the human, in the liver and kidneys, from the essential amino acids lysine and methionine. [1][2][3] In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium-and long-chain esters, such as acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC), is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. [1][2][3] L-carnitine has important roles in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane; more than 90% of the human body's store is present in skeletal and cardiac muscle. 1,2 L-carnitine is an essen-ORIGINAL RESEARCH

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Section: Discussionmentioning

confidence: 65%

“…19 Intravenous injection of PLC not only increases the plasma concentrations of PLC, it also elevates plasma concentrations and urinary excretion of L-carnitine and ALC. 20 In our study there was also an increase in the plasma levels, and the area under the curve of ALC and PLC within two hours after the oral administration of L-carnitine.…”

Section: Discussionmentioning

confidence: 94%

Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Cao¹,

Wang²,

Liu³

et al. 2009

CIM

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“…Immediately before (0 h) and at 0.5, 1.0, 1.5, 2, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 12.0 and 24.0 h after oral administration of L-carnitine (2.0 g in 200 ml warm water) (Sahajwalla et al 1995), 3 ml venous blood was collected and transferred into a chilled tube, which was centrifuged (2,300 g for 5 min) within 10 min to separate the plasma. The plasma was transferred into a polypropylene tube, which was kept at −20°C for analysis.…”

Section: Methodsmentioning

confidence: 99%

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Cao

et al. 2011

Tohoku J. Exp. Med.

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L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 μmol/L. After single oral administration, the maximum plasma concentration (C max ) and area under the curve (AUC 0-∞ ) were 84.7 ± 25.2 μmol/L and 2,676.4 ± 708.3 μmol/L·h, respectively. The half-life and the time required to reach the C max was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

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“…Humans synthesize approximately 1-2 micromole of carnitine/kg/day [52]. Carnitine synthesis is a multi-step process that occurs in various human tissues including the kidney, liver, heart, muscle, and brain [53].…”

Section: What Is Carnitine?mentioning

confidence: 99%

“…In several observational studies, it was noted that individuals on high carnitine diets (Ͼ6 grams) had approximately 5-15% absorption, while those on a low load diet of carnitine (Ͻ1 g), such as a vegan diet, had greater than 75% of the carnitine absorbed [52,90,91]. This apparent limit in absorptive capacity may limit the clinical effects on an overdose of oral L-carnitine.…”

Section: Is L-carnitine Safe?mentioning

confidence: 99%

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

Katiyar

Aaron

2007

J. Med. Toxicol.

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A 28-year-old African-American male was found unresponsive outside of his girlfriend's house around 7 o'clock in the morning. He spent the night at the girlfriend's house and was last witnessed to be awake about 12 hours earlier. The girlfriend and her family were unable to awaken the patient and called emergency medical services (EMS). There was no history of headache, dizziness, fever, chills, nausea, vomiting, seizures, trauma, depressive thoughts, or suicidal ideation. When EMS arrived, they administered 6 mg of naloxone intramuscularly without effect, and the patient was transported to the emergency department (ED).After arriving in the ED, the cardiac monitor displayed a narrow-complex rhythm with a rate of 85-90 per minute. His initial vital signs were: heart rate 91/min; blood pressure 148/80 mmHg; respiratory rate 24/min; temperature 35.1°C (95.1°F) rectally; and pulse oximetry 100% on non-rebreather face mask oxygen. A fingerstick glucose determination was 106 mg/dL.Physical examination revealed a well developed, well nourished individual who was obtunded and unresponsive. His pupils were 2 mm, unreactive to light, and without nystagmus. He had diffuse bilateral wheezing, regular heart rate without any murmurs, and decreased bowel sounds. The patient had warm skin with good distal pulses in all extremities and no cyanosis, erythema, or edema. There was no clonus or hyperreflexia, and the gag reflex was intact.His past medical history was only pertinent for an old gunshot wound to the head. He developed a seizure disorder and was taking divalproex, 500 mg BID. Reportedly, he was allergic to carbamazepine and phenytoin. The patient smoked cigarettes, but the family stated that he had no history of alcohol or illicit drug use.A 12-lead electrocardiogram showed a sinus rhythm with a rate of 92 bpm, a PR interval of 134 msec, a QRS duration of 90 msec, and a QTc of 601 msec. A head CT and chest radiograph were unremarkable. Laboratory tests were obtained.

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Multiple‐Dose Pharmacokinetics and Bioequivalence L-Carnitine 330-mg Tablet versus 1-g Chewable Tablet versus Enteral Solution in Healthy Adult Male Volunteers

Cited by 39 publications

References 11 publications

Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Comparison of pharmacokinetics of L-carnitine, Acetyl-L-carnitine and Propionyl-Lcarnitine after single oral administration of L-carnitine in healthy volunteers

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Case files of the Children’s Hospital of Michigan Regional Poison Control Center: The use of carnitine for the management of acute valproic acid toxicity

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