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Identification
Name Clarithromycin
Accession Number DB01211 (APRD00181)
Type small molecule
Groups approved
Description

Clarithromycin, a semisynthetic macrolide antibiotic derived from erythromycin, inhibits bacterial protein synthesis by binding to the bacterial 50S ribosomal subunit. Binding inhibits peptidyl transferase activity and interferes with amino acid translocation during the translation and protein assembly process. Clarithromycin may be bacteriostatic or bactericidal depending on the organism and drug concentration.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • CLA
  • Clarithromycine
  • Clathromycin
Brand names
  • Biaxin
  • Biaxin XL
  • Klacid
  • Klaricid
  • Macladin
  • Naxy
  • Veclam
  • Zeclar
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Other Macrolides
  • Protein Synthesis Inhibitors
  • Macrolides
CAS number 81103-11-9
Weight Average: 747.9534
Monoisotopic: 747.476891299
Chemical Formula C38H69NO13
InChI Key InChIKey=AGOYDEPGAOXOCK-FEXCRMSXSA-N
InChI
InChI=1S/C38H69NO13/c1-15-26-38(10,45)31(42)21(4)28(40)19(2)17-37(9,47-14)33(52-35-29(41)25(39(11)12)16-20(3)48-35)22(5)30(23(6)34(44)50-26)51-27-18-36(8,46-13)32(43)24(7)49-27/h19-27,29-33,35,41-43,45H,15-18H2,1-14H3/t19-,20-,21+,22+,23-,24-,25+,26-,27-,29-,30+,31-,32-,33-,35+,36+,37-,38-/m1/s1
Plain Text
IUPAC Name
(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-6-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-14-ethyl-12,13-dihydroxy-4-{[(2S,4S,5R,6R)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7-methoxy-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecane-2,10-dione
SMILES
CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@@H]2C[C@](C)(OC)[C@H](O)[C@@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@@](C)(C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O)OC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication An alternative medication for the treatment of acute otitis media caused by H. influenzae, M. catarrhalis, or S. pneumoniae in patients with a history of type I penicillin hypersensitivity. Also for the treatment of pharyngitis and tonsillitis caused by susceptible Streptococcus pyogenes, as well as respiratory tract infections including acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, mild to moderate community-acquired pneuomia, Legionnaires' disease, and pertussis. Other indications include treatment of uncomplicated skin or skin structure infections, helicobacter pylori infection, duodenal ulcer disease, bartonella infections, early Lyme disease, and encephalitis caused by Toxoplasma gondii (in HIV infected patients in conjunction with pyrimethamine). Clarithromycin may also decrease the incidence of cryptosporidiosis, prevent the occurence of α-hemolytic (viridans group) streptococcal endocarditis, as well as serve as a primary prevention for Mycobacterium avium complex (MAC) bacteremia or disseminated infections (in adults, adolescents, and children with advanced HIV infection).
Pharmacodynamics Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, some mycobacteria, and some other organisms including Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. Other aerobic bacteria that clarithromycin has activity against include C. pneumoniae and M. pneumoniae. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.
Mechanism of action Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.
Absorption Clarithromycin is well-absorbed, acid stable and may be taken with food.
Volume of distribution Not Available
Protein binding ~ 70% protein bound
Metabolism

Hepatic - predominantly metabolized by CYP3A4 resulting in numerous drug interactions.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 14-hydroxyclarithromycin hydroxylation 20 2301.82
Cytochrome P450 3A4 N-desmethylclarithromycin N-demethylation 11 12503
Route of elimination After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is somewhat greater, approximately 30%.
Half life 3-4 hours
Clearance Not Available
Toxicity Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort. Transient hearing loss with high doses has been observed. Pseudomembraneous colitis has been reported with clarithromycin use. Allergic reactions ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis and Stevens-Johnson syndrome have also occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually reversible, but fatalities have been reported. Clarithromycin may also cause tooth decolouration which may be removed by dental cleaning. Fetal abnormalities, such as cardiovascular defects, cleft palate and fetal growth retardation, have been observed in animals. Clarithromycin may cause QT prolongation.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00248 Clarithromycin Pathway SMP00248
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Abbott laboratories
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc florida
  • Apotex corp
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Wockhardt ltd
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Biaxin 60 250 mg tablet Bottle 379.5 USD bottle
Clarithromycin 250 mg/5ml Suspension 100ml Bottle 86.23 USD bottle
Clarithromycin 250 mg/5ml Suspension 50ml Bottle 46.56 USD bottle
Clarithromycin 125 mg/5ml Suspension 100ml Bottle 45.24 USD bottle
Clarithromycin 125 mg/5ml Suspension 50ml Bottle 27.99 USD bottle
Biaxin XL 500 mg 24 Hour tablet 6.77 USD tablet
Biaxin xl 500 mg tablet 6.57 USD tablet
Biaxin 250 mg tablet 6.42 USD tablet
Biaxin 500 mg tablet 6.37 USD tablet
Clarithromycin 500 mg 24 Hour tablet 5.21 USD tablet
Clarithromycin er 500 mg tablet 5.01 USD tablet
Clarithromycin 250 mg tablet 4.61 USD tablet
Clarithromycin 500 mg tablet 4.61 USD tablet
Biaxin Bid 500 mg Tablet 3.41 USD tablet
Biaxin Xl 500 mg Extended-Release Tablet 2.63 USD tablet
Mylan-Clarithromycin 500 mg Tablet 1.91 USD tablet
Pms-Clarithromycin 500 mg Tablet 1.91 USD tablet
Ratio-Clarithromycin 500 mg Tablet 1.91 USD tablet
Sandoz Clarithromycin 500 mg Tablet 1.91 USD tablet
Biaxin Bid 250 mg Tablet 1.73 USD tablet
Clarithromycin 100% powder 1.56 USD g
Biaxin 50 mg/ml Suspension 0.59 USD ml
Biaxin 25 mg/ml Suspension 0.3 USD ml
Patents
Country Patent Number Approved Expires
United States 6551616 1997-07-15 2017-07-15
United States 6010718 1997-04-11 2017-04-11
Canada 2471102 2005-02-08 2017-07-25
Canada 1328609 1994-04-19 2011-04-19
Properties
State solid
Melting point 217 - 220 oC
Experimental Properties
Property Value Source
water solubility 0.33 mg/L PhysProp
logP 1.7 PhysProp
pKa 8.99 Various sources
Predicted Properties
Property Value Source
water solubility 2.17e-01 g/l ALOGPS
logP 3.18 ALOGPS
logP 3.24 ChemAxon Molconvert
logS -3.54 ALOGPS
pKa 12.94 ChemAxon Molconvert
hydrogen acceptor count 13 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 182.91 ChemAxon Molconvert
rotatable bond count 8 ChemAxon Molconvert
refractivity 190.79 ChemAxon Molconvert
polarizability 81.46 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H: Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet. 2007 Feb 10;369(9560):482-90. Pubmed
  2. Zuckerman JM, Qamar F, Bono BR: Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline. Infect Dis Clin North Am. 2009 Dec;23(4):997-1026, ix-x. Pubmed
  3. Piscitelli SC, Danziger LH, Rodvold KA: Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm. 1992 Feb;11(2):137-52. Pubmed
  4. Peters DH, Clissold SP: Clarithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic potential. Drugs. 1992 Jul;44(1):117-64. Pubmed
  5. Clarithromycin. Tuberculosis (Edinb). 2008 Mar;88(2):92-5. Pubmed
  6. Stephenson GA, Stowell JG, Toma PH, Pfeiffer RR, Byrn SR: Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity. J Pharm Sci. 1997 Nov;86(11):1239-44. Pubmed
External Links
Resource Link
KEGG Drug D00276 Link_out
KEGG Compound C06912 Link_out
ChEBI 3732 Link_out
ChEMBL 3732 Link_out
Therapeutic Targets Database DAP000410 Link_out
Drug Product Database 2244756 Link_out
RxList http://www.rxlist.com/cgi/generic/clarith.htm Link_out
Drugs.com http://www.drugs.com/clarithromycin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Clarithromycin Link_out
ATC Codes
  • J01FA09
AHFS Codes
  • 08:12.12.92
PDB Entries Not Available
FDA label show (376.3 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Biaxin - take without regard to meals (however absorption appears to be improved when drug is taken with food).
  • Biaxin XL - take with a meal, taking it on an empty stomach is associated with total product exposure 30% inferior to that observed when administered with food.
Targets

1. 50S ribosomal protein L10

Pharmacological action: yes
Actions: inhibitor

Protein L10 is also a translational repressor protein. It controls the translation of the rplJL-rpoBC operon by binding to its mRNA

Organism class: bacterial
UniProt ID: P0A7J6 Link_out
Gene: rplJ
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Morimura T, Hashiba M, Kameda H, Takami M, Takahama H, Ohshige M, Sugawara F: Identification of macrolide antibiotic-binding Human_p8 protein. J Antibiot (Tokyo). 2008 May;61(5):291-6. Pubmed
  4. Champney WS, Burdine R: Macrolide antibiotic inhibition of translation and 50S ribosomal subunit assembly in methicillin-resistant Staphylococcus aureus cells. Microb Drug Resist. 1998 Fall;4(3):169-74. Pubmed
  5. Zuckerman JM, Qamar F, Bono BR: Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline. Infect Dis Clin North Am. 2009 Dec;23(4):997-1026, ix-x. Pubmed
  6. Clarithromycin. Tuberculosis (Edinb). 2008 Mar;88(2):92-5. Pubmed
  7. Champney WS, Burdine R: Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus. Antimicrob Agents Chemother. 1995 Sep;39(9):2141-4. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zuckerman JM, Qamar F, Bono BR: Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline. Infect Dis Clin North Am. 2009 Dec;23(4):997-1026, ix-x. Pubmed
  2. Clarithromycin. Tuberculosis (Edinb). 2008 Mar;88(2):92-5. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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. Epub 2009 Nov 24. Pubmed
  5. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. Pubmed

2. Cytochrome P450 3A5

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C19

Actions: substrate, inhibitor

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 imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1A2

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  3. Egashira K, Ohtani H, Itoh S, Koyabu N, Tsujimoto M, Murakami H, Sawada Y: Inhibitory effects of pomelo on the metabolism of tacrolimus and the activities of CYP3A4 and P-glycoprotein. Drug Metab Dispos. 2004 Aug;32(8):828-33. Pubmed
  4. Clarithromycin. Tuberculosis (Edinb). 2008 Mar;88(2):92-5. Pubmed
  5. Dey S, Gunda S, Mitra AK: Pharmacokinetics of erythromycin in rabbit corneas after single-dose infusion: role of P-glycoprotein as a barrier to in vivo ocular drug absorption. J Pharmacol Exp Ther. 2004 Oct;311(1):246-55. Epub 2004 Jun 2. Pubmed

2. Solute carrier family 22 member 7

Actions: inhibitor

Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

UniProt ID: Q9Y694 Link_out
Gene: SLC22A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Kobayashi Y, Sakai R, Ohshiro N, Ohbayashi M, Kohyama N, Yamamoto T: Possible involvement of organic anion transporter 2 on the interaction of theophylline with erythromycin in the human liver. Drug Metab Dispos. 2005 May;33(5):619-22. Epub 2005 Feb 11. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 20, 2011 13:35

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.