Identification

Name
Gliclazide
Accession Number
DB01120  (APRD00460)
Type
Small Molecule
Groups
Approved
Description

Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic β cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).

Structure
Thumb
Synonyms
  • 1-(3-Azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea
  • 1-(Hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea
  • Gliclazida
  • Gliclazidum
  • N-(4-Methylbenzenesulfonyl)-N'-(3-azabicyclo(3.3.0)oct-3-yl)urea
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DiamicronTablet80 mgOralServier1990-12-31Not applicableCanada
Diamicron MrTablet, extended release60 mgOralServier2010-12-09Not applicableCanada
Diamicron MrTablet, extended release30 mgOralServier2001-04-04Not applicableCanada
GlicTablet80 mgOralPrempharm Inc2003-10-022005-08-05Canada
GliclazideTablet80 mgOralSanis Health Inc2010-02-25Not applicableCanada
Gliclazide -tab 80mgTablet80 mgOralProval Pharma Division Of Servier Canada Inc1997-08-132012-02-13Canada
Gliclazide-80Tablet80 mgOralPro Doc Limitee2003-12-10Not applicableCanada
Sandoz GliclazideTablet80 mgOralSandoz Canada Incorporated2004-08-092008-08-07Canada
Sandoz Gliclazide MrTablet, extended release30 mgOralSandoz Canada Incorporated2017-06-02Not applicableCanada
Sandoz Gliclazide MrTablet, extended release60 mgOralSandoz Canada Incorporated2017-06-02Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-gliclazideTablet80 mgOralApotex Corporation2002-07-02Not applicableCanada
Apo-gliclazide MrTablet, extended release60 mgOralApotex Corporation2015-04-14Not applicableCanada
Apo-gliclazide MrTablet, extended release30 mgOralApotex Corporation2008-06-04Not applicableCanada
Ava-gliclazideTablet80 mgOralAvanstra Inc2011-08-112014-08-21Canada
Gpc-gliclazide MrTablet, extended release30 mgOralGeneric Partners (Canada) Inc.2015-03-31Not applicableCanada
Gpc-gliclazide MrTablet, extended release60 mgOralGeneric Partners (Canada) Inc.Not applicableNot applicableCanada
Mint-gliclazide MrTablet, extended release30 mgOralMint Pharmaceuticals Inc2014-06-02Not applicableCanada
Mint-gliclazide MrTablet, extended release60 mgOralMint Pharmaceuticals Inc2016-11-14Not applicableCanada
Mylan-gliclazideTablet80 mgOralMylan Pharmaceuticals1998-08-13Not applicableCanada
Mylan-gliclazide MrTablet, extended release30 mgOralMylan Pharmaceuticals2015-08-07Not applicableCanada
International/Other Brands
Diamicron (Servier) / Glimicron / Nordialex
Categories
UNII
G4PX8C4HKV
CAS number
21187-98-4
Weight
Average: 323.411
Monoisotopic: 323.130362243
Chemical Formula
C15H21N3O3S
InChI Key
BOVGTQGAOIONJV-UHFFFAOYSA-N
InChI
InChI=1S/C15H21N3O3S/c1-11-5-7-14(8-6-11)22(20,21)17-15(19)16-18-9-12-3-2-4-13(12)10-18/h5-8,12-13H,2-4,9-10H2,1H3,(H2,16,17,19)
IUPAC Name
1-(4-methylbenzenesulfonyl)-3-{octahydrocyclopenta[c]pyrrol-2-yl}urea
SMILES
CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CC2CCCC2C1

Pharmacology

Indication

For the treatment of NIDDM in conjunction with diet and exercise.

Associated Conditions
Pharmacodynamics

Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.

Mechanism of action

Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.

TargetActionsOrganism
AATP-binding cassette sub-family C member 8
binder
Human
UVascular endothelial growth factor A
other/unknown
Human
Absorption

Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.

Volume of distribution
Not Available
Protein binding

94%, highly bound to plasma proteins

Metabolism

Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates.

Route of elimination

Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).

Half life

10.4 hours. Duration of action is 10-24 hours.

Clearance
Not Available
Toxicity

LD50=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Gliclazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYP2C19*2(A;A) / (A;G)681G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with reduction in gliclazide metabolism.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>AEffect Directly StudiedThe presence of this polymorphism in CYP2C19 is associated with reduction in gliclazide metabolism.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*4Not Available1A>GEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*6Not Available395G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GEffect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE may increase the hypoglycemic activities of Gliclazide.
2,4-thiazolidinedione2,4-thiazolidinedione may increase the hypoglycemic activities of Gliclazide.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypoglycemic activities of Gliclazide.
AbirateroneThe metabolism of Gliclazide can be decreased when combined with Abiraterone.
AcarboseAcarbose may increase the hypoglycemic activities of Gliclazide.
AcebutololAcebutolol may increase the hypoglycemic activities of Gliclazide.
AcenocoumarolGliclazide may increase the anticoagulant activities of Acenocoumarol.
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Gliclazide.
Acetyl sulfisoxazoleThe metabolism of Gliclazide can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Gliclazide.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals. A consistent diet is recommended to reduce the risk of hypoglycemia.

References

Synthesis Reference

U.S. Patent 3,501,495

General References
Not Available
External Links
Human Metabolome Database
HMDB0015252
KEGG Drug
D01599
PubChem Compound
3475
PubChem Substance
46505475
ChemSpider
3356
ChEBI
31654
ChEMBL
CHEMBL427216
Therapeutic Targets Database
DAP000522
PharmGKB
PA10892
Wikipedia
Gliclazide
ATC Codes
A10BB09 — Gliclazide
AHFS Codes
  • 68:20.20 — Sulfonylureas
MSDS
Download (57.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentEpilepsies1
1WithdrawnNot AvailableComparative Bioavailability1
2CompletedTreatmentPsoriasis / Type 2 Diabetes Mellitus1
3CompletedTreatmentType 2 Diabetes Mellitus4
3RecruitingTreatmentDiabetes Mellitus (DM)1
3TerminatedNot AvailableCoronary and Peripheral Endothelial Dysfunction1
4CompletedTreatmentDiabetes Mellitus (DM)2
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4CompletedTreatmentBone destruction / Menopause / Osteopenia / Type 2 Diabetes Mellitus1
4CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD) / Type2 Diabetes1
4CompletedTreatmentType 2 Diabetes Mellitus6
4Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
4RecruitingPreventionDiabetic Nephropathies / Type 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentType 2 Diabetes Mellitus1
4WithdrawnTreatmentAngina Pectoris / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus2
Not AvailableRecruitingOtherType 2 Diabetes Mellitus1
Not AvailableUnknown StatusTreatmentType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, extended releaseOral60 mg
Tablet, extended releaseOral30 mg
TabletOral80 mg
Prices
Unit descriptionCostUnit
Diamicron 80 mg Tablet0.42USD tablet
Apo-Gliclazide 80 mg Tablet0.23USD tablet
Gliclazide 80 mg Tablet0.23USD tablet
Mylan-Gliclazide 80 mg Tablet0.23USD tablet
Novo-Gliclazide 80 mg Tablet0.23USD tablet
Pms-Gliclazide 80 mg Tablet0.23USD tablet
Diamicron Mr 30 mg Sustained-Release Tablet0.16USD tablet
Apo-Gliclazide Mr 30 mg Sustained-Release Tablet0.15USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2273420No2002-07-092019-05-27Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180-182U.S. Patent 3,501,495
logP2.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.19 mg/mLALOGPS
logP1.52ALOGPS
logP1.73ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
pKa (Strongest Basic)1.38ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.51 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity83.88 m3·mol-1ChemAxon
Polarizability34.22 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9944
Blood Brain Barrier+0.8445
Caco-2 permeable-0.6543
P-glycoprotein substrateSubstrate0.6982
P-glycoprotein inhibitor INon-inhibitor0.8619
P-glycoprotein inhibitor IINon-inhibitor0.931
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateSubstrate0.6226
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6925
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9218
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8751
Ames testNon AMES toxic0.8047
CarcinogenicityNon-carcinogens0.7944
BiodegradationNot ready biodegradable0.7997
Rat acute toxicity2.0016 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5992
hERG inhibition (predictor II)Non-inhibitor0.8064
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Tosyl compounds / Benzenesulfonyl compounds / Sulfonylureas / Semicarbazides / Pyrrolidines / Organosulfonic acids and derivatives / Aminosulfonyl compounds / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Benzenesulfonamide / Tosyl compound / Benzenesulfonyl group / Toluene / Sulfonylurea / Pyrrolidine / Semicarbazide / Organic sulfonic acid or derivatives / Aminosulfonyl compound / Sulfonyl
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-sulfonylurea (CHEBI:31654)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Sulfonylurea receptor activity
Specific Function
Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
Gene Name
ABCC8
Uniprot ID
Q09428
Uniprot Name
ATP-binding cassette sub-family C member 8
Molecular Weight
176990.36 Da
References
  1. Gribble FM, Ashcroft FM: Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism. 2000 Oct;49(10 Suppl 2):3-6. [PubMed:11078468]
  2. Harrower A: Gliclazide modified release: from once-daily administration to 24-hour blood glucose control. Metabolism. 2000 Oct;49(10 Suppl 2):7-11. [PubMed:11078469]
  3. Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM: Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia. 2001 Aug;44(8):1019-25. [PubMed:11484080]
  4. Reimann F, Ashcroft FM, Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9. [PubMed:11574406]
  5. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. [PubMed:12475777]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Vascular endothelial growth factor receptor binding
Specific Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
Molecular Weight
27042.205 Da
References
  1. Mamputu JC, Renier G: Advanced glycation end products increase, through a protein kinase C-dependent pathway, vascular endothelial growth factor expression in retinal endothelial cells. Inhibitory effect of gliclazide. J Diabetes Complications. 2002 Jul-Aug;16(4):284-93. [PubMed:12126787]
  2. Mamputu JC, Renier G: Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide. Diabetes Obes Metab. 2004 Mar;6(2):95-103. [PubMed:14746574]
  3. Li L, Renier G: Activation of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase by advanced glycation end products links oxidative stress to altered retinal vascular endothelial growth factor expression. Metabolism. 2006 Nov;55(11):1516-23. [PubMed:17046555]
  4. Kimura T, Takagi H, Suzuma K, Kita M, Watanabe D, Yoshimura N: Comparisons between the beneficial effects of different sulphonylurea treatments on ischemia-induced retinal neovascularization. Free Radic Biol Med. 2007 Aug 1;43(3):454-61. Epub 2007 May 3. [PubMed:17602961]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Zhang Y, Si D, Chen X, Lin N, Guo Y, Zhou H, Zhong D: Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects. Br J Clin Pharmacol. 2007 Jul;64(1):67-74. Epub 2007 Feb 12. [PubMed:17298483]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Igaki A, Kobayashi K, Kimura M, Sakoguchi T, Matsuoka A: Influence of blood proteins on biomedical analysis. XII. Effects of glycation on gliclazide (oral hypoglycemic drug)-binding with serum albumin in diabetics. Chem Pharm Bull (Tokyo). 1992 Jan;40(1):255-7. [PubMed:1576681]
  2. Kobayashi K, Kimura M, Sakoguchi T, Hase A, Matsuoka A: Influence of blood proteins on biomedical analysis. V. Effect of ethyl alcohol on gliclazide-binding with bovine serum albumin. Chem Pharm Bull (Tokyo). 1982 Mar;30(3):1077-80. [PubMed:7094168]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2018 22:30