Levetiracetam
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| Systematic (IUPAC) name | |
| (S)-2-(2-oxopyrrolidin-1-yl)butanamide | |
| Clinical data | |
| Trade names | Keppra |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a699059 |
| Pregnancy cat. | C(US) |
| Legal status | ℞ Prescription only |
| Routes | Oral, intravenous |
| Pharmacokinetic data | |
| Bioavailability | ~100% |
| Protein binding | <10% |
| Metabolism | Enzymatic hydrolysis of acetamide group |
| Half-life | 6 - 8 hr |
| Excretion | Urinary |
| Identifiers | |
| CAS number | 102767-28-2  |
| ATC code | N03AX14 |
| PubChem | CID 5284583 |
| DrugBank | DB01202 |
| ChemSpider | 4447633 |
| UNII | 44YRR34555 |
| KEGG | D00709 |
| ChEMBL | CHEMBL1286 |
| Chemical data | |
| Formula | C8H14N2O2 |
| Mol. mass | 170.209 g/mol |
| SMILES | eMolecules & PubChem |
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Levetiracetam (INN) (
/lɛvɨtɪˈræsɨtæm/) is an anticonvulsant medication used to treat epilepsy.[1] It is the S-enantiomer of etiracetam, structurally similar to the prototypical nootropic drug piracetam.
Levetiracetam is marketed under the trade name Keppra. Keppra is manufactured by UCB Pharmaceuticals Inc. Since November 2008 the drug has been available as a generic brand in the United States.
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[edit] Medical uses
Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures, or as an adjunctive therapy for partial, myoclonic and tonic-clonic seizures.[2] It is also used in veterinary medicine for similar purposes.
Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, autism, bipolar disorder and anxiety disorder, but its most serious adverse effects are behavioral and its benefit-risk ratio in these conditions is not well understood.[3]
Along with other anticonvulsants like gabapentin, it is also sometimes used to treat neuropathic pain. It has not been found to be useful for essential tremors.[4]
[edit] Adverse effects
Levetiracetam is, in general, well tolerated[5] but may cause drowsiness, weakness, unsteady gait, coordination problems, headache, pain, forgetfulness, anxiety, irritability or agitation, dizziness, mood changes, nervousness, loss of appetite, vomiting, diarrhea, constipation, and changes in skin pigmentation (color).
Some serious side effects can be depression, hallucinations, suicidal thoughts, seizures that are worse or different, fever, sore throat, and other signs of infection, double vision, itching, rash, swelling of the face. A study published in 2005 suggests that the addition of pyridoxine (vitamin B6) may curtail some of the psychiatric symptoms.[6]
[edit] Measurement in bodily fluids
[edit] Assay of Levetiracetam[7]
There are only a few papers published reporting therapeutic drug monitoring methods of levetiracetam. Three of them employed HPLC with UV-detection,[8][9] ,[10] and two methods were using GC with NPD-detection,.[9][11] Microemulsion electrokinetic chromatography with UV-detection was utilized in one method.[12] Two methods facilitating chiral separation of the S- and Renantiomer of levetiracetam, one utilizing GC–MS and the other HPLC–UV, were published,.[13][14] These methods were designed to investigate in dogs the pharmacokinetic and pharmacodynamic properties of the two enantiomers separately. For routine therapeutic drug monitoring in men, these methods were not appropriate. In all but one of the methods,[10] sample preparation with SPE or liquid–liquid extraction is necessary. Pucci et al.[10] evaluated the feasibility of protein precipitation as the only sample preparation step in comparison to SPE. They concluded, that protein precipitation is a suitable and fast sample preparation for measuring routine patient samples.
Various HPLC,[15][16],[17][18],[19][20],[21] and LC-MS,[22][23][24] methods have been reported for the determination of levetiracetam in pure and pharmaceutical dosage forms.
[edit] Mechanism of action
The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle protein, SV2A,[25] which is believed to impede nerve conduction across synapses.[26]
[edit] Available forms
- ready-to-administer bags of Sodium Chloride Injection, at concentrations of 500 mg/100 mL, 1000 mg/100 mL and 1500 mg/100 mL[27]
[edit] See also
[edit] References
- ^ Abou-Khalil B (June 2008). "Levetiracetam in the treatment of epilepsy". Neuropsychiatr Dis Treat 4 (3): 507–23. PMC 2526377. PMID 18830435. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2526377.
- ^ BNF 59. BMA & RPSGB. 2010.
- ^ Farooq MU, Bhatt A, Majid A, Gupta R, Khasnis A, Kassab MY (2009). "Levetiracetam for managing neurologic and psychiatric disorders". Am J Health Syst Pharm 66 (6): 541–61. doi:10.2146/ajhp070607. PMID 19265183.
- ^ http://www.neurology.org/content/early/2011/10/18/WNL.0b013e318236f0fd.abstract
- ^ Gambardella A, Labate A, Colosimo E, Ambrosio R, Quattrone A (February 2008). "Monotherapy for partial epilepsy: focus on levetiracetam". Neuropsychiatr Dis Treat 4 (1): 33–8. PMC 2515905. PMID 18728811. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2515905.
- ^ "Clinical Epilepsy: Pediatrics". Epilepsia 46 (s8): 142–67. 2005. doi:10.1111/j.1528-1167.2005.460801_16.x. http://www3.interscience.wiley.com/journal/118734483/abstract.
- ^ Prafulla Kumar Sahu, M. Mathrusri Annapurna; Analytical Method development by Liquid Chromatography, LAP LAMBERT Academic Publishing GmbH & Co. KG, Germany, ISBN 978-3-8443-2869-1.
- ^ N. Ratnaraj, H.C. Doheny, P.N. Patsalos, Ther. Drug Monit. 18 (1996) 154.
- ^ a b T.A. Vermeij, P.M. Edelbroek, J. Chromatogr. B Biomed. Appl. 662 (1994) 134.
- ^ a b c V. Pucci, F. Bugamelli, R. Mandrioli, A. Ferranti, E. Kenndler, M.A. Raggi, Biomed. Chromatogr. 18 (2004) 37.
- ^ R. Coupez, R. Straetemans, G. Sehgal, A. Stockis, Z.S. Lu, J. Clin. Pharmacol. 43 (2003) 1370.
- ^ M. Ivanova, A. Piunti, E. Marziali, N. Komarova, M.A. Raggi, E. Kenndler, Electrophoresis 24 (2003) 992.
- ^ N. Isoherranen, M. Roeder, S. Soback, B. Yagen, V. Schurig, M. Bialer, J. Chromatogr. B Biomed. Sci. Appl. 745 (2000) 325.
- ^ N. Isoherranen, B. Yagen, S. Soback, M. Roeder, V. Schurig, M. Bialer, Epilepsia 42 (2001) 825.
- ^ Prafulla Kumar Sahu*, Dillip Kumar Sahoo, M.M.Annapurna, M.E.Bhanoji Rao, Development and validation of an RP-HPLC method for determination of Levetiracetam in Bulk and Pharmaceutical Dosage Forms, Analytical Chemistry: An Indian Journal, 2009, 8(1).
- ^ C. Manuela, M. Susan, A. Fiorenzo, R. Roberto and B. Agostino, J chromatogr B., 2008, 873(1), 129.
- ^ N. Appala Raja, J. Venkateswara Rao, K. Vanitha Prakash, K. Mukkanti and K. Srinivasu, E Journal of Chemistry, 2008, 5(S2), 1098.
- ^ J. Valarmathy, L. Samueljoshua, G. Rathinavel, C. Selvin Thanija and T. Sivakumar,Research J Pharm and Tech., 2008, 1(3), 395.
- ^ J. Marten Lobenhoffer and S.M. Bode Boger, J Chromatogr B., 2005, 815, 197.
- ^ N. Ratnaraj, C. Doheny Helen and N. Patsalos Philip, Ther Drug Monit, 1996, 18(2), 154.
- ^ A.C. Vermeij and P.M. Edelbroek, J Chromatogr B., 1994, 662,134.
- ^ M. Kamal Matar, J Pharm Biomed Anal., 2008, 48(3), 822.
- ^ G. Saravanan, G. Jhothy, Y. Suresh, A. Annerao, M. Ramakrishna, M. Yogeshwar Reddy and B. Ravibabu, Chromatographia, 2008, 67, 173.
- ^ Tiedong Guo, M. Lisa Oswald, M. Damodara Rao and J. Steven Soldin, Clinica Chimica Acta, 2007, 375, 115.
- ^ Lynch BA, Lambeng N, Nocka K, et al. (June 2004). "The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam". Proc Natl Acad Sci USA. 101 (26): 9861–6. doi:10.1073/pnas.0308208101. PMC 470764. PMID 15210974. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=470764.
- ^ Rogawski, MA (June 2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Research 69 (3): 273–94. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526. PMID 16621450. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1562526.
- ^ "Mylan Inc. (MYL) Launches Innovative Version of Antiepileptic Drug Levetiracetam", ClinicaSpace (Mylan), 20 Jan 2012, http://www.clinicaspace.com/news_story.aspx?NewsEntityId=246929, retrieved 22 Jan 2012
[edit] External links
- PubMed Health A division of the National Library of Medicine at the National Institutes of Health.
- Keppra (levetiracetam) Final Printed Label April 2009. Center for Drug Evaluation and Research, U.S. Food and Drug Administration. Accessed 29 July 2011.
- Keppra UCB (manufacturer's website)
- NIH MedLine drug information
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