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End Stage Renal Disease (ESRD) patients on maintenance hemodialysis may have low plasma carnitine concentrations and an increased ratio of acylcarnitine/carnitine because of reduced intake of meat and dairy products, reduced renal synthesis and dialytic losses. Certain clinical conditions common in hemodialysis patients such as malaise, muscle weakness, cardiomyopathy and cardiac arrhythmias may be related to abnormal carnitine metabolism. The recommended starting dose is 10 to 20 mg/kg dry body weight as a slow 2 to 3 minute bolus injection into the venous return line after each dialysis session. Initiation of therapy may be prompted by trough (pre-dialysis) plasma levocarnitine concentrations that are below normal (40 to 50 µmol/L). Dose adjustments should be guided by trough (pre-dialysis) levocarnitine concentrations, and downward dose adjustments (e.g. to 5 mg/kg after dialysis) may be made as early as the third or fourth week of therapy. Singarajah C, Carlson RW. A review of the role of blood lactate measurements in the ICU. J Intensive Care Med. 1998;13(5):218–28.
Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran Acemetacin may decrease the excretion rate of Levocarnitine which could result in a higher serum level. Kong JY, Rabkin SW: Lovastatin does not accentuate but is rather additive to palmitate-induced apoptosis in cardiomyocytes. Prostaglandins Leukot Essent Fatty Acids. 2002 Nov;67(5):293-302. [ Article] Jogl G, Tong L: Crystal structure of carnitine acetyltransferase and implications for the catalytic mechanism and fatty acid transport. Cell. 2003 Jan 10;112(1):113-22. [ Article] According to the National Institutes of Health, carnitine interacts with pivalate-conjugated antibiotics such as pivampicillin which are used in the treatment of urinary tract infections. Taking these antibiotics increases the excretion of pivaloyl-carnitine, which can lead to carnitine depletion. Carnitine also interacts with the anticonvulsants valproic acid, phenobarbital, phenytoin, or carbamazepine. Taking these have been shown to significantly decrease blood levels of carnitine. In addition, the use of valproic acid with or without other anticonvulsants may cause hepatotoxicity and increase plasma ammonia concentrations, leading to encephalopathy. Some common side effects include:Bohmer, T., Rydning, A. and Solberg, H.E. 1974. Carnitine levels in human serum in health and disease. Marzo, A., Arrigoni Martelli, E., Mancinelli, A., Cardace, G., Corbelletta, C., Bassani, E. and Solbiati, M. 1991. Protein binding of L-carnitine family components. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [ Article] In a relative bioavailability study in 15 healthy adult male volunteers levocarnitine tablets were found to be bio-equivalent to levocarnitine oral solution. Following 4 days of dosing with 6 tablets of levocarnitine 330 mg b.i.d. or 2 g of levocarnitine oral solution twice daily, the maximum plasma concentration (C max) was about 80 μmol/L and the time to maximum plasma concentration (T max) occurred at 3.3 hours.
Christiansen, R., Bremer, J. 1976. Active transport of butyrobetaine and carniitine into isolated liver cells. Biochim. Biophys. Acta 448:562-577.A prospective, double-blind, randomized controlled trial was implemented in a medical ICU. Participants were 54 patients, aged > 18 years, with multiple conditions, randomly assigned to receive 3 g l-carnitine per day or placebo, along with enteral feeding, for 1 week. Primary outcomes included monitoring variables related to nutritional status. Result It is advisable to monitor therapy by measuring free and acyl carnitine levels in both plasma and urine. 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. The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide.
Levocarnitine was not bound to plasma protein or albumin when tested at any concentration or with any species including the human. ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. ( 23092397) Spectra Mass Spec (NIST) Not Available Spectra Spectrum
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Noguchi, J. and Sakota, N.; US. Patent 3,135,788; June 2,1964; assigned to Nihon Zoki Seiyaku Kabushikikaisha (Japan). Lindstedt, S. and Lindstedt, G. 1961. Distribution and excretion of carnitine in the rat. Acta Chem. Scand. 15:701-702.
The absolute bioavailability of levocarnitine from the two oral formulations of levocarnitine, calculated after correction for circulating endogenous plasma concentrations of levocarnitine, was 15.1% ± 5.3% for levocarnitine tablets and 15.9% ± 4.9% for levocarnitine oral solution. In a similar study in ESRD patients also receiving 20 mg/kg CARNITOR ® 3 times per week after hemodialysis, 12- and 24-week mean pre-dialysis (trough) levocarnitine concentrations were 189 (N=25) and 243 (N=23) μmol/L, respectively. 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. Hypersensitivity Reactions Tamai I, Ohashi R, Nezu JI, Sai Y, Kobayashi D, Oku A, Shimane M, Tsuji A: Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem. 2000 Dec 22;275(51):40064-72. [ Article]The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Levocarnitine.
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