Identification

Name
Lacosamide
Accession Number
DB06218
Type
Small Molecule
Groups
Approved
Description

Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, and is indicated for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain. Recent studies indicate that Lacosamide only affects those neurons which are depolarized or active for long periods of time, typical of neurons at the focus of an epileptic seizure, as opposed to other antiepileptic drugs such as carbamazepine or lamotrigine which slow the recovery from inactivation and reduce the ability of neurons to fire action potentials.

Structure
Thumb
Synonyms
  • Erlosamide
  • Harkoseride
  • Lacosamida
External IDs
ADD 243037 / ADD-243037 / SPM 927 / SPM-927
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VimpatTablet, film coated50 mgOralUcb Pharma Sa2008-08-29Not applicableEu
VimpatTablet, film coated150 mg/1OralUcb Inc2009-05-26Not applicableUs
VimpatTablet, film coated100 mgOralUcb Pharma Sa2008-08-29Not applicableEu
VimpatTablet, film coated50 mgOralUcb Pharma Sa2008-08-29Not applicableEu
VimpatInjection, solution10 mg/mlIntravenousUcb Pharma Sa2008-08-29Not applicableEu
VimpatTablet, film coated100 mg/1OralRemedy Repack2017-03-01Not applicableUs
VimpatTablet, film coated200 mgOralUcb Pharma Sa2008-08-29Not applicableEu
VimpatSolution10 mgIntravenousUcb Inc2011-09-20Not applicableCanada
VimpatInjection10 mg/1mLIntravenousUCB, Inc.2008-11-122008-11-12Us
VimpatTablet100 mgOralUcb Inc2010-10-21Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LacosamideTablet, film coated150 mg/1OralNatco Pharma Limited2016-05-28Not applicableUs
LacosamideSolution10 mg/1mLOralAmneal Pharmaceuticals of New York Llc2013-11-29Not applicableUs
LacosamideTablet, film coated200 mg/1OralBreckenridge Pharmaceutical, Inc.2016-06-15Not applicableUs
LacosamideTablet, film coated50 mg/1OralBreckenridge Pharmaceutical, Inc.2016-06-15Not applicableUs
LacosamideTablet, film coated100 mg/1OralNatco Pharma Limited2016-05-28Not applicableUs
LacosamideTablet, film coated150 mg/1OralBreckenridge Pharmaceutical, Inc.2016-06-15Not applicableUs
LacosamideTablet, film coated200 mg/1OralNatco Pharma Limited2016-05-28Not applicableUs
LacosamideTablet, film coated50 mg/1OralNatco Pharma Limited2016-05-28Not applicableUs
LacosamideTablet, film coated100 mg/1OralBreckenridge Pharmaceutical, Inc.2016-06-15Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
VimpatLacosamide (50 mg/1) + Lacosamide (100 mg/1)KitUcb Inc2009-05-26Not applicableUs
VimpatLacosamide (50 mg/1) + Lacosamide (100 mg/1)KitUcb Inc2009-05-26Not applicableUs
International/Other Brands
Vimpat
Categories
UNII
563KS2PQY5
CAS number
175481-36-4
Weight
Average: 250.2936
Monoisotopic: 250.131742452
Chemical Formula
C13H18N2O3
InChI Key
VPPJLAIAVCUEMN-GFCCVEGCSA-N
InChI
InChI=1S/C13H18N2O3/c1-10(16)15-12(9-18-2)13(17)14-8-11-6-4-3-5-7-11/h3-7,12H,8-9H2,1-2H3,(H,14,17)(H,15,16)/t12-/m1/s1
IUPAC Name
(2R)-N-benzyl-2-acetamido-3-methoxypropanamide
SMILES
COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1

Pharmacology

Indication

Lacosamide is indicated for adjunctive therapy for partial onset seizures in patients with epilepsy over 17 years old. Injection is indicated for short term use when oral therapy is not feasible.

Associated Conditions
Pharmacodynamics

Lacosamide therapy is correlated with a decrease in seizure frequency. It should be noted that in group analyses, dosages above 400 mg/day do not appear to result in additional benefit.

Mechanism of action

It is proposed that lacosamide's inhibition of sodium channels is responsible for analgesia. Lacosamide may be selective for inhibiting depolarized neurons rather than neurons with normal resting potentials. Pain and nociceptor hyperexcitability are associated with neural membrane depolarization. Lacosamide binds to collapsin response mediator protein-2 (CRMP-2), a phosphoprotein which is expressed primarily in the nervous system and is involved in neuronal differentiation and control of axonal outgrowth. The role CRMP-2 of binding in seizure control is hasn't been elucidated.

TargetActionsOrganism
USodium channel protein type 9 subunit alphaNot AvailableHuman
USodium channel protein type 3 subunit alphaNot AvailableHuman
USodium channel protein type 10 subunit alphaNot AvailableHuman
Absorption

Lacosamide has a negligible first pass effect with bioavailability of about 100%. The maximum Lacosamide plasma concentrations occur about 1-4 hours after oral administration, and the pharmacokinetics of Lacosamide are dose proportional. Food does not affect absorption.

Volume of distribution

approximately 0.6 L/kg; thus close to the volume of total body water.

Protein binding

<15%

Metabolism

Lacosamide is a CYP2C19 substrate. The relative contribution of other CYP isoforms or non-CYP enzymes in the metabolism of lacosamide is not known. Primary compounds excreted were unchanged lacosamide (approximately 40% of the dose), its O-desmethyl metabolite (approximately 30%), and a structurally unknown polar fraction (~20%). The plasma exposure of the major human metabolite, O-desmethyl-lacosamide, is approximately 10% of that of lacosamide. This metabolite has no known pharmacological activity.

Route of elimination

Lacosamide is eliminated primarily from the systemic circulation by biotransformation and renal excretion.

Half life

13 Hours

Clearance

95% recovered in the urine 0.5% in the feces

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all Effect InferredReduced O-desmethyl metabolite concentrations in plasma.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GEffect InferredReduced O-desmethyl metabolite concentrations in plasma.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lacosamide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lacosamide.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Lacosamide is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineLacosamide may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Lacosamide.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lacosamide.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Lacosamide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lacosamide.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lacosamide.
5-androstenedioneThe metabolism of Lacosamide can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

Synthesis Reference

http://www.google.com/patents?id=IIanAAAAEBAJ&pg=PA2&source=gbsselectedpages&cad=3#v=onepage&q&f=false

General References
  1. Sheets PL, Heers C, Stoehr T, Cummins TR: Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J Pharmacol Exp Ther. 2008 Jul;326(1):89-99. doi: 10.1124/jpet.107.133413. Epub 2008 Mar 31. [PubMed:18378801]
  2. Jones GL, Popli GS, Silvia MT: Lacosamide-induced valproic acid toxicity. Pediatr Neurol. 2013 Apr;48(4):308-10. doi: 10.1016/j.pediatrneurol.2012.12.039. [PubMed:23498565]
External Links
KEGG Drug
D07299
PubChem Compound
219078
PubChem Substance
175427063
ChemSpider
189902
BindingDB
50300204
ChEBI
135939
ChEMBL
CHEMBL58323
PharmGKB
PA166160048
Wikipedia
Lacosamide
ATC Codes
N03AX18 — Lacosamide
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
FDA label
Download (276 KB)
MSDS
Download (570 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableEpilepsies1
1CompletedNot AvailableHealthy Volunteers4
1CompletedNot AvailableHealthy Volunteers / Impaired Renal Function1
1CompletedOtherHealthy Male Chinese Volunteers1
1CompletedOtherHealthy Male Volunteers1
1CompletedTreatmentHealthy Volunteers1
1RecruitingTreatmentAlcohol Use Disorder (AUD)1
1, 2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedPreventionMigraines1
2CompletedTreatmentEpilepsies5
2CompletedTreatmentEpilepsy, Localization Related1
2CompletedTreatmentFibromyalgia Syndrome1
2CompletedTreatmentNonconvulsive Seizures1
2CompletedTreatmentPainful Diabetic Neuropathy (PDN)2
2CompletedTreatmentPostherpetic Neuralgia2
2CompletedTreatmentChronic, refractory Neuropathic Pain1
2Enrolling by InvitationTreatmentEpilepsies1
2Not Yet RecruitingTreatmentGlioma of Brain / Gliomas / Neoplasms, Brain1
2TerminatedTreatmentEpilepsy, Localization Related1
2TerminatedTreatmentOsteoarthritis (OA)1
2WithdrawnTreatmentAvascular Necrosis / Osteoarthritis (OA) / Rheumatoid Arthritis1
2, 3CompletedTreatmentDiabetic Neuropathies2
2, 3CompletedTreatmentEpilepsy, Localization Related1
2, 3RecruitingTreatmentEpilepsies1
3Active Not RecruitingTreatmentEpilepsies1
3Active Not RecruitingTreatmentEpilepsies / Partial onset seizure Epilepsy1
3CompletedTreatmentDiabetic Neuropathies2
3CompletedTreatmentEpilepsies7
3CompletedTreatmentEpilepsies / Monotherapy2
3CompletedTreatmentEpilepsies / Partial onset seizure Epilepsy3
3CompletedTreatmentEpilepsy, Localization Related1
3CompletedTreatmentEpilepsy, Localization Related / Partial onset seizure Epilepsy2
3CompletedTreatmentPainful Diabetic Neuropathy (PDN)2
3CompletedTreatmentPartial Seizures With or Without Secondary Generalization1
3CompletedTreatmentSmall Fibre Neuropathy1
3Enrolling by InvitationTreatmentEpilepsies2
3RecruitingTreatmentEpilepsies1
3RecruitingTreatmentEpilepsy With Partial-onset Seizures1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentEpilepsy, Localization Related1
3Unknown StatusTreatmentEpilepsies1
3WithdrawnTreatmentEpilepsies / Refractory seizure disorders1
4CompletedTreatmentEpilepsies2
4CompletedTreatmentEpilepsy, Localization Related3
4RecruitingTreatmentAcute Kidney Injury (AKI) / Impaired Renal Function / Pharmacokinetics / Renal Failure1
4TerminatedTreatmentSeizures1
Not AvailableActive Not RecruitingTreatmentBrain Cancer1
Not AvailableAvailableNot AvailableEpilepsy, Localization Related1
Not AvailableCompletedNot AvailableEpilepsies2
Not AvailableCompletedNot AvailableEpilepsy With Partial Onset Seizures With or Without Secondary Generalization1
Not AvailableCompletedNot AvailableEpilepsy, Localization Related1
Not AvailableCompletedNot AvailableFocal Epilepsy With and Without Secondary Generalization1
Not AvailableCompletedNot AvailableSeizures1
Not AvailableCompletedBasic ScienceHealthy Male Volunteers1
Not AvailableTerminatedPreventionTraumatic Brain Injury (TBI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionOral10 mg/1mL
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral200 mg/1
InjectionIntravenous10 mg/1mL
Injection, solutionIntravenous10 mg/ml
Kit
SolutionIntravenous10 mg
SyrupOral10 mg/ml
TabletOral100 mg
TabletOral150 mg
TabletOral200 mg
TabletOral50 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral150 mg
Tablet, film coatedOral200 mg
Tablet, film coatedOral50 mg
Tablet, film coatedOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5654301No1997-08-052014-08-05Us
USRE38551No2004-07-062022-03-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)140-146˚Chttp://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500064326.pdf
boiling point (°C)536.447 °C at 760 mmHgACD/Labs
water solubilityLacosamide is a white to light yellow powder. It is sparingly soluble in water and slightly soluble in acetonitrile and ethanol.FDA Label
logP0.728ACD/Labs
Predicted Properties
PropertyValueSource
Water Solubility0.465 mg/mLALOGPS
logP0.18ALOGPS
logP-0.022ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)12.47ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.43 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity67.57 m3·mol-1ChemAxon
Polarizability26.68 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9771
Blood Brain Barrier+0.7181
Caco-2 permeable-0.6886
P-glycoprotein substrateSubstrate0.7158
P-glycoprotein inhibitor INon-inhibitor0.6904
P-glycoprotein inhibitor IINon-inhibitor0.8878
Renal organic cation transporterNon-inhibitor0.8757
CYP450 2C9 substrateNon-substrate0.8732
CYP450 2D6 substrateNon-substrate0.7634
CYP450 3A4 substrateNon-substrate0.6572
CYP450 1A2 substrateNon-inhibitor0.8084
CYP450 2C9 inhibitorNon-inhibitor0.8704
CYP450 2D6 inhibitorNon-inhibitor0.8775
CYP450 2C19 inhibitorNon-inhibitor0.8201
CYP450 3A4 inhibitorNon-inhibitor0.837
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9732
Ames testNon AMES toxic0.7694
CarcinogenicityNon-carcinogens0.8388
BiodegradationNot ready biodegradable0.8499
Rat acute toxicity2.1629 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9678
hERG inhibition (predictor II)Non-inhibitor0.8489
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (18.4 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Alpha amino acid amides / Benzene and substituted derivatives / Acetamides / Secondary carboxylic acid amides / Dialkyl ethers / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Monocyclic benzene moiety / Benzenoid / Acetamide / Carboxamide group / Secondary carboxylic acid amide / Dialkyl ether / Ether / Organic nitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated sodium channel activity
Specific Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
Gene Name
SCN9A
Uniprot ID
Q15858
Uniprot Name
Sodium channel protein type 9 subunit alpha
Molecular Weight
226370.175 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated sodium channel activity
Specific Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...
Gene Name
SCN3A
Uniprot ID
Q9NY46
Uniprot Name
Sodium channel protein type 3 subunit alpha
Molecular Weight
226291.905 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated sodium channel activity
Specific Function
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference acro...
Gene Name
SCN10A
Uniprot ID
Q9Y5Y9
Uniprot Name
Sodium channel protein type 10 subunit alpha
Molecular Weight
220623.605 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Contin M, Albani F, Riva R, Candela C, Mohamed S, Baruzzi A: Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013 Dec;35(6):849-52. doi: 10.1097/FTD.0b013e318290eacc. [PubMed:23942540]
  2. Bentue-Ferrer D, Tribut O, Verdier MC: [Therapeutic drug monitoring of lacosamide]. Therapie. 2012 Mar-Apr;67(2):151-5. doi: 10.2515/therapie/2012012. Epub 2012 Aug 2. [PubMed:22850102]
  3. Chung SS: New treatment option for partial-onset seizures: efficacy and safety of lacosamide. Ther Adv Neurol Disord. 2010 Mar;3(2):77-83. doi: 10.1177/1756285609355850. [PubMed:21179600]
  4. Drugs.com Lacosamide Monograph [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Abou-Khalil BW: Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4. doi: 10.1111/j.1535-7511.2009.01317.x. [PubMed:19826503]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Abou-Khalil BW: Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4. doi: 10.1111/j.1535-7511.2009.01317.x. [PubMed:19826503]

Drug created on March 19, 2008 10:17 / Updated on November 17, 2018 07:21