Identification
- Summary
Dirithromycin is an antibiotic used to treat a variety of respiratory, skin, and other infections.
- Generic Name
- Dirithromycin
- DrugBank Accession Number
- DB00954
- Background
Dirithromycin is a macrolide glycopeptide antibiotic used to treat many different types of bacterial infections, such as bronchitis, pneumonia, tonsillitis, and even skin infections.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Dirithromycin (DB00954)
- Weight
- Average: 835.086
Monoisotopic: 834.5453052 - Chemical Formula
- C42H78N2O14
- Synonyms
- (9S)-9-deoxo-11-deoxy-9,11-(imino((1R)-2-(2-methoxyethoxy)ethylidene)oxy)erythromycin
- Dirithromycin
- Dirithromycine
- Dirithromycinum
- Diritromicina
- External IDs
- LY 237216
- LY-237216
Pharmacology
- Indication
For the treatment of the following mild-to-moderate infections caused by susceptible strains of microorganisms: acute bacterial exacerbations of chronic bronchitis, secondary bacterial infection of acute bronchitis, community-acquired pneumonia, pharyngitis/tonsilitis, and uncomplicated skin and skin structure infections.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute exacerbation of chronic bronchitis (aecb) •••••••••••• ••••••• ••••••• ••••••• Treatment of Acute exacerbation of chronic bronchitis (aecb) •••••••••••• ••••••• ••••••• ••••••• Treatment of Community acquired pneumonia (cap) •••••••••••• ••••••• ••••••• ••••••• Treatment of Lower respiratory tract infection (lrti) •••••••••••• ••••••• ••••••• ••••••• Treatment of Lower respiratory tract infection (lrti) •••••••••••• ••••••• ••••••• ••••••• - Contraindications & Blackbox Warnings
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Dirithromycin is a pro-drug which is converted non-enzymatically during intestinal absorption into the microbiologically active moiety erythromycylamine. Erythromycylamine exerts its activity by binding to the 50S ribosomal subunits of susceptible mircoorganisms resulting in inhibition of protein synthesis. Dirithromycin/erythromycylamine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections: Staphylococcus aureus (methicillin-susceptible strains only), Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, and Mycoplasma pneumoniae.
- Mechanism of action
Dirithromycin prevents bacteria from growing, by interfering with their protein synthesis. Dirithromycin binds to the 50S subunit of the 70S bacterial ribosome, and thus inhibits the translocation of peptides. Dirithromycin has over 10 times higher affinity to the subunit 50S than erythromycin. In addition, dirithromycin binds simultaneously in to two domains of 23S RNA of the ribosomal subunit 50S, where older macrolides bind only in one. Dirithromycin can also inhibit the formation of ribosomal subunits 50S and 30S.
Target Actions Organism A23S ribosomal RNA inhibitorEnteric bacteria and other eubacteria - Absorption
Oral dirithromycin is rapidly absorbed, with an absolute bioavailability of approximately 10%. Dietary fat has little or no effect on the bioavailability of dirithromycin.
- Volume of distribution
Not Available
- Protein binding
15 to 30% for erythromycylamine, the active compound.
- Metabolism
Dirithromycin is converted by nonenzymatic hydrolysis during absorption to the active compound, erythromycylamine. Sixty to 90% of a dose is hydrolyzed to erythromycylamine within 35 minutes after dosing, and conversion is nearly complete after 1.5 hours. Erythromycylamine undergoes little or no hepatic biotransformation. No other metabolites of dirithromycin have been detected in the serum.
- Route of elimination
Not Available
- Half-life
The mean plasma half-life of erythromycylamine was estimated to be about 8 h (2 to 36 h), with a mean urinary terminal elimination half-life of about 44 h (16 to 65 h) in patients with normal renal function.
- Clearance
Not Available
- Adverse Effects
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The toxic symptoms following an overdose of a macrolide antibiotic may include nausea, vomiting, epigastric distress, and diarrhea.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Dirithromycin. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Dirithromycin. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Dirithromycin. Acetyldigitoxin The serum concentration of Acetyldigitoxin can be increased when it is combined with Dirithromycin. Albendazole The metabolism of Albendazole can be decreased when combined with Dirithromycin. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Dynabac
Categories
- ATC Codes
- J01FA13 — Dirithromycin
- Drug Categories
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibacterials for Systemic Use
- Antiinfectives for Systemic Use
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Lactones
- Macrolides
- Macrolides, Lincosamides and Streptogramins
- Polyketides
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- Aminoglycosides
- Alternative Parents
- Macrolides and analogues / O-glycosyl compounds / Oxanes / 1,3-oxazinanes / Monosaccharides / Tertiary alcohols / Trialkylamines / Secondary alcohols / Amino acids and derivatives / 1,2-aminoalcohols show 13 more
- Substituents
- 1,2-aminoalcohol / 1,3-oxazinane / Acetal / Alcohol / Aliphatic heteropolycyclic compound / Amine / Amino acid or derivatives / Aminoglycoside core / Azacycle / Carbonyl group show 26 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- macrolide antibiotic (CHEBI:474014)
- Affected organisms
- Enteric bacteria and other eubacteria
Chemical Identifiers
- UNII
- 1801D76STL
- CAS number
- 62013-04-1
- InChI Key
- WLOHNSSYAXHWNR-DWIOZXRMSA-N
- InChI
- InChI=1S/C42H78N2O14/c1-15-29-42(10,49)37-24(4)32(43-30(56-37)21-52-17-16-50-13)22(2)19-40(8,48)36(58-39-33(45)28(44(11)12)18-23(3)53-39)25(5)34(26(6)38(47)55-29)57-31-20-41(9,51-14)35(46)27(7)54-31/h22-37,39,43,45-46,48-49H,15-21H2,1-14H3/t22-,23-,24+,25+,26-,27+,28+,29-,30-,31+,32+,33-,34+,35+,36-,37-,39+,40-,41-,42-/m1/s1
- IUPAC Name
- (1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,15R,17S)-9-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-3-ethyl-2,10-dihydroxy-7-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-15-[(2-methoxyethoxy)methyl]-2,6,8,10,12,17-hexamethyl-4,16-dioxa-14-azabicyclo[11.3.1]heptadecan-5-one
- 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)(O)C[C@@H](C)[C@@H]2N[C@@H](COCCOC)O[C@H]([C@H]2C)[C@]1(C)O
References
- Synthesis Reference
Counter FT, Ensminger PW, Preston DA, Wu CY, Greene JM, Felty-Duckworth AM, Paschal JW, Kirst HA: Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin. Antimicrob Agents Chemother. 1991 Jun;35(6):1116-26. Pubmed.
- General References
- Brogden RN, Peters DH: Dirithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994 Oct;48(4):599-616. [Article]
- Wintermeyer SM, Abdel-Rahman SM, Nahata MC: Dirithromycin: a new macrolide. Ann Pharmacother. 1996 Oct;30(10):1141-9. [Article]
- Sides GD, Cerimele BJ, Black HR, Busch U, DeSante KA: Pharmacokinetics of dirithromycin. J Antimicrob Chemother. 1993 Mar;31 Suppl C:65-75. [Article]
- External Links
- KEGG Drug
- D03865
- PubChem Compound
- 6473883
- PubChem Substance
- 46509156
- ChemSpider
- 4976073
- BindingDB
- 59397
- 23437
- ChEBI
- 474014
- ChEMBL
- CHEMBL1237072
- ZINC
- ZINC000096095661
- Therapeutic Targets Database
- DAP000888
- PharmGKB
- PA449368
- PDBe Ligand
- DI0
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Dirithromycin
- PDB Entries
- 6of1 / 6xz7 / 6xza / 6xzb
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 1 Completed Treatment Healthy Subjects (HS) 4 0 Terminated Treatment Osteomyelitis 1
Pharmacoeconomics
- Manufacturers
- Lilly research laboratories
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Tablet, coated Tablet, delayed release 250 mg Tablet, delayed release - Prices
Unit description Cost Unit Dynabac D5-Pak 10 250 mg Enteric Coated Tabs Box 43.54USD box Dynabac D5-Pak 250 mg Enteric Coated Tabs 4.35USD tab DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Poor Not Available logP 1.6 Not Available - Predicted Properties
Property Value Source Water Solubility 0.23 mg/mL ALOGPS logP 2.9 ALOGPS logP 2.95 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 12.49 Chemaxon pKa (Strongest Basic) 9.13 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 15 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 196.33 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 212.95 m3·mol-1 Chemaxon Polarizability 90.75 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.6028 Blood Brain Barrier - 0.9704 Caco-2 permeable - 0.7573 P-glycoprotein substrate Substrate 0.8808 P-glycoprotein inhibitor I Inhibitor 0.7564 P-glycoprotein inhibitor II Non-inhibitor 0.6712 Renal organic cation transporter Non-inhibitor 0.8978 CYP450 2C9 substrate Non-substrate 0.8537 CYP450 2D6 substrate Non-substrate 0.9117 CYP450 3A4 substrate Substrate 0.7329 CYP450 1A2 substrate Non-inhibitor 0.9305 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9051 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9141 Ames test Non AMES toxic 0.7677 Carcinogenicity Non-carcinogens 0.9345 Biodegradation Not ready biodegradable 0.9961 Rat acute toxicity 2.7997 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9944 hERG inhibition (predictor II) Non-inhibitor 0.5956
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 273.73212 predictedDeepCCS 1.0 (2019) [M+H]+ 275.45584 predictedDeepCCS 1.0 (2019) [M+Na]+ 281.68143 predictedDeepCCS 1.0 (2019)
Targets
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Zhanel GG, Dueck M, Hoban DJ, Vercaigne LM, Embil JM, Gin AS, Karlowsky JA: Review of macrolides and ketolides: focus on respiratory tract infections. Drugs. 2001;61(4):443-98. [Article]
- Parsad D, Pandhi R, Dogra S: A guide to selection and appropriate use of macrolides in skin infections. Am J Clin Dermatol. 2003;4(6):389-97. [Article]
- Williams JD, Sefton AM: Comparison of macrolide antibiotics. J Antimicrob Chemother. 1993 Mar;31 Suppl C:11-26. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. doi: 10.2165/00003088-200039030-00003. [Article]
- Westphal JF: Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin. Br J Clin Pharmacol. 2000 Oct;50(4):285-95. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:46