Delving into the Latest Updates on Dirithromycin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(9S)-9-deoxo-11-deoxy-9,11-(imino((1R)-2-(2-methoxyethoxy)ethylidene)oxy)erythromycin, Dirithromycin (USP/INN), Divitross

+ [18]

Target

50S subunit

Mechanism

50S subunit inhibitors(50S ribosomal subunit inhibitors)

Therapeutic Areas

Infectious DiseasesMouth and Tooth DiseasesOtorhinolaryngologic Diseases+ [2]

Active Indication

Acute BronchitisLegionellosisMycoplasma Infections+ [2]

Inactive Indication

Bronchitis, ChronicCommunity Acquired PneumoniaNon-complicated skin and skin structure infection+ [2]

Originator Organization

Eli Lilly & Co.

Active Organization-

Inactive Organization

Lilly Research Laboratories

Almirall SA

Drug Highest PhaseApproved

First Approval Date

FR (11 Oct 1993),

Bacterial Infections

Regulation-

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Structure

Molecular FormulaC42H78N2O14

InChIKeyWLOHNSSYAXHWNR-DWIOZXRMSA-N

CAS Registry62013-04-1

Comparative, Randomized, Two -Period, Two-treatment, Two -Sequence, Open Label, Crossover Bioequivalence Pilot Study of Dirithromycin 500 mg Enteric Coated Tablet (One Tablet) of (Abdi İbrahim İlaç San. Ve Tic. A. Ş., Turkey) Versus Dynabac 250 mg Enteric Coated Tablet (Two Tablets) of (Abdi İbrahim İlaç San. Ve Tic. A. Ş., Turkey) in Healthy Subjects Under Fasting Conditions.

To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Erythromycylamine and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation.

Start Date01 Jun 2014

Sponsor / Collaborator

Pharmaceutical Research Unit, Jordan

[+1]

NCT02185846 / CompletedPhase 1IIT

Comparative, Randomized, Two -Period, Two-treatment, Two -Sequence, Open Label, Crossover Bioequivalence Pilot Study of Dirithromycin 500 mg Enteric Coated Tablet (One Tablet) of (Abdi İbrahim İlaç San. Ve Tic. A. Ş., Turkey) Versus Dynabac 250 mg Enteric Coated Tablet (Two Tablets) of (Abdi İbrahim İlaç San. Ve Tic. A. Ş., Turkey) in Healthy Subjects Under Fed Conditions.

To assess the bioequivalence of the investigational TEST product with the marketed REFERENCE products by measurement of Plasma concentrations of Erythromycylamine and calculation of the bioequivalence parameters from those measurements followed by ANOVA and 90% confidence interval statistical evaluation.

Start Date01 Jun 2014

Sponsor / Collaborator

Pharmaceutical Research Unit, Jordan

[+1]

100 Clinical Results associated with Dirithromycin

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100 Translational Medicine associated with Dirithromycin

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100 Patents (Medical) associated with Dirithromycin

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157

Literatures (Medical) associated with Dirithromycin

10 Oct 2023·Biosensors-Basel

Immunotechniques for the Group Determination of Macrolide Antibiotics Traces in the Environment Using a Volume-Mediated Sensitivity Enhancement Strategy.

Article

Author: Bychkova, Elena N ; Melekhin, Artem O ; Galvidis, Inna A ; Burkin, Maksim A ; Tevyashova, Anna N

Macrolide antibiotics, which are effective antimicrobial agents, are intensively used in human and veterinary medicine, as well as in agriculture. Consequently, they are found all over the world as environmental pollutants, causing harm to sensitive ecological communities and provoking a selection of resistant forms. A novel azithromycin derivative, which was used as hapten conjugate, ensured the group immunorecognition of six major macrolide representatives (105-41%), namely erythromycin, erythromycin ethylsuccinate, clarithromycin, roxithromycin, azithromycin, and dirithromycin in a competitive immunoassay based on anti-clarithromycin antibodies. The heterologous hapten-based ELISA format resulted in a 5-fold increase in sensitivity, with an IC₅₀ value of 0.04 ng/mL for erythromycin. In this study, we proposed an underexploited strategy in an immunoassay field to significantly improve the detectability of analytes in environmental samples. Unlike most approaches, it does not require special enhancers/amplifiers or additional concentration/extraction procedures; instead, it involves analyzing a larger volume of test samples. A gradual volume increase in the samples (from 0.025 to 10 mL) analyzed using a direct competitive ELISA, immunobeads, and immunofiltration assay formats based on the same reagents resulted in a significant improvement (more than 50-fold) in assay sensitivity and detection limit up to 5 and 1 pg/mL, respectively. The suitability of the test for detecting the macrolide contamination of natural water was confirmed by the recovery of macrolides from spiked blank samples (71.7-141.3%). During 2022-2023, a series of natural water samples from Lake Onega and its influents near Petrozavodsk were analyzed, using both the developed immunoassay and HPLC-MS/MS. The results revealed no contamination of macrolide antibiotic.

01 Sep 2020·Journal of pharmaceutical and biomedical analysisQ3 · MEDICINE

Development of a latex particles-based lateral flow immunoassay for group determination of macrolide antibiotics in breast milk

Q3 · MEDICINE

Article

Author: Schneider, Rudolf J ; Galvidis, Inna A ; Eremin, Sergei A ; Burkin, Maksim A ; Raysyan, Anna

A lateral flow immunoassay (LFIA) using latex particles labeled with antibody to BSA-clarithromycin (CLA) was developed for the rapid simultaneous group determination of six macrolide antibiotics. Optimization of antigen spotting on the membrane and latex probe loading allowed improving visual detectability (vLOD) 100 times, which was 1, 1, 10, 10, 50, and 1000 ng/mL for CLA, roxithromycin, erythromycin, dirithromycin, azithromycin, and oleandomycin in buffer, respectively. The calculated limits of instrumental detection (cLOD) were respectively 0.12, 0.15, 1.4, 2.1, 2.4, and 3.3 ng/mL. To avoid a strong influence of breast milk of a very diverse and variable composition, a sample pretreatment is proposed. The six macrolides mentioned can be visually detected in breast milk after 20 min pretreatment at concentrations of 10-1000 ng/mL or instrumentally with cLOD of 4.0, 2.5, 30, 42, 42 and 180 ng/mL. The recovery rate from the spiked samples carried out using a strip scanner device ranged from 71 % to 110 %, and precision expressed as relative standard deviation was between 3-14 %. The described rapid on-site diagnostic assay format can be useful for monitoring the content of antibiotics in breast milk during macrolide treatment to ensure safe breastfeeding of infants.

01 Jun 2020·RNA (New York, N.Y.)Q3 · BIOLOGY

Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to the E. coli 70S ribosome

Q3 · BIOLOGY

Article

Author: Komarova, Ekaterina S ; Polikanov, Yury S ; Dontsova, Olga A ; Pichkur, Evgeny B ; Shiriaev, Dmitrii I ; Myasnikov, Alexander G ; Konevega, Andrey L ; Bogdanov, Alexey A ; Kasatsky, Pavel ; Tereshchenkov, Andrey G ; Sergiev, Petr V ; Paleskava, Alena ; Osterman, Ilya A

Macrolides are one of the most successful and widely used classes of antibacterials, which kill or stop the growth of pathogenic bacteria by binding near the active site of the ribosome and interfering with protein synthesis. Dirithromycin is a derivative of the prototype macrolide erythromycin with additional hydrophobic side chain. In our recent study, we have discovered that the side chain of dirithromycin forms lone pair-π stacking interaction with the aromatic imidazole ring of the His69 residue in ribosomal protein uL4 of the Thermus thermophilus 70S ribosome. In the current work, we found that neither the presence of the side chain, nor the additional contact with the ribosome, improve the binding affinity of dirithromycin to the ribosome. Nevertheless, we found that dirithromycin is a more potent inhibitor of in vitro protein synthesis in comparison with its parent compound, erythromycin. Using high-resolution cryo-electron microscopy, we determined the structure of the dirithromycin bound to the translating Escherichia coli 70S ribosome, which suggests that the better inhibitory properties of the drug could be rationalized by the side chain of dirithromycin pointing into the lumen of the nascent peptide exit tunnel, where it can interfere with the normal passage of the growing polypeptide chain.

100 Deals associated with Dirithromycin

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External Link

KEGG	Wiki	ATC	Drug Bank
D03865	Dirithromycin	J01FA13	DB00954

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Bronchitis	US	Lilly Research Laboratories	19 Jun 1995
Bronchitis, Chronic	US	Lilly Research Laboratories	19 Jun 1995
Community Acquired Pneumonia	US	Lilly Research Laboratories	19 Jun 1995
Non-complicated skin and skin structure infection	US	Lilly Research Laboratories	19 Jun 1995
Pharyngitis	US	Lilly Research Laboratories	19 Jun 1995
Pneumonia	US	Lilly Research Laboratories	19 Jun 1995
Skin Diseases, Infectious	US	Lilly Research Laboratories	19 Jun 1995
Acute Bronchitis	US	Lilly Research Laboratories	19 Jun 1995
Tonsillitis	US	Lilly Research Laboratories	19 Jun 1995
Bacterial Infections	FR	Almirall SA	11 Oct 1993
Legionellosis	CN	-	-
Mycoplasma Infections	CN	-	-
Staphylococcus Aureus Infections	CN	-	-