80214-83-1 Usage
Description
Roxithromycin, an oxime ether derivative of erythromycin, is a new macrolide antibiotic of high potency and long duration. It belongs to the new generation of macrolide antibiotics and is a semisynthetic erythromycin derivative with improved acid stability. Its in vitro activity spectrum is similar to that of erythromycin but is superior against Legionella, Mycoplasma, and Chlamydia. Roxithromycin is a white crystalline powder, odorless, with a bitter taste, and is easily soluble in ethanol or acetone, more easily soluble in methanol or ether, but almost insoluble in water.
Uses
Used in Human Medicine:
Roxithromycin is used as an antibiotic for the treatment of respiratory tract infections, such as pneumonia, acute bronchitis, acute infection of chronic bronchitis, atypical pneumonia, and genitourinary system infections, skin, and soft tissue infections. It has a strong bactericidal effect on Gram-negative bacteria and some Gram-negative bacteria (meningococcus, Neisseria gonorrhoeae, influenza bacilli, pertussis, Brucella) and spirochetes, Mycoplasma pneumoniae, and Rickettsia. It exhibits good therapeutic effect and tolerance with smaller adverse reactions than erythromycin.
Used in Veterinary Medicine:
In veterinary clinical practice, Roxithromycin is used for the treatment of penicillin-resistant Staphylococcus aureus caused severe infection, pneumonia, uterine inflammation, and poultry chronic respiratory disease. It is the first-choice drug for the treatment of drug-resistance Staphylococcus aureus and hemolytic streptococcus. It is also used for the treatment of livestock and poultry chronic respiratory disease with good efficacy in the treatment of livestock and poultry Staphylococcus and Streptococcus disease, Chlamydia, spirochetal disease (swine dysentery), infectious pleurisy, and rhinitis.
Used in Pharmaceutical Industry:
Roxithromycin is used as an active pharmaceutical ingredient in the development of antibiotics for both human and veterinary medicine. It is known for its excellent oral absorption, quick efficacy, stronger bioavailability, and higher plasma concentrations than erythromycin. Its half-life is up to 12 hours, which is longer than that of erythromycin (1.5-2.0 hours). The brand name for Roxithromycin is Rulide (Hoechst-Roussel).
Pharmacological effects
Roxithromycin is a semi-synthetic 14-membered ring macrolide antibiotic. It has similar mechanism of action as erythromycin with its antibacterial effect in vivo being 1-4 times stronger than erythromycin. Its effect against Gram-positive bacteria is slightly worse than erythromycin; the effect against Legionella pneumophila is somehow stronger than erythromycin; for Chlamydia pneumoniae, Mycoplasma pneumoniae and Ureaplasma urealyticum, it has similar or slightly stronger antimicrobial effect compared with erythromycin.
This product can penetrate through the bacterial cell membrane, having reversible binding to bacterial ribosomes 50S subunit at close to the donor ("P" position), blocking the transfer of ribonucleic acid binding to the "P" position as well as blocking the transfer of the peptide chain from the acceptor position ("A" position) to "P" position, thus leading to the inhibition of bacterial protein synthesis and playing an antibacterial effect. It is characterized by faster access to macrophages, alveolar cells and neutrophils. In vitro studies have shown that roxithromycin has broad antibacterial spectrum with similar effect as erythromycin against a variety of Streptococcus (including A, B, C-type streptococcus and Streptococcus pneumoniae, but except G-type and enterococci), Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus aureus (except MRSA), Staphylococcus epidermidis, Legionella pneumophila, Haemophilus ducreyi, Chlamydia trachomatis, Mycoplasma pneumoniae and oral or vaginal anaerobic bacteria. Neisseria catarrhalis is highly sensitive to roxithromycin. It also has inhibitory effects on Campylobacter, Bordetella pertussis, Haemophilus influenzae, Mycobacterium tuberculosis and Diphtheria bacilli but has no antibacterial activity against other gram-negative bacteria. The in vivo antibacterial activity of this product was significantly stronger than that of erythromycin. It also has significant effect against chlamydia, mycoplasma, ureaplasma urealyticum, Treponema pallidum and Legionella infection. It also has relatively weak effect on the helicobacter, Neisseria gonorrhoeae, meningococcal and Bordetella pertussis. Some bacteria have cross-resistance to erythromycin and this product.
Indications
This product is applicable to the purulent Streptococcus caused pharyngitis and tonsillitis, susceptible bacteria-caused sinusitis, otitis media, acute bronchitis, acute exacerbation of chronic bronchitis, Mycoplasma pneumoniae or Chlamydia pneumoniae caused pneumonia; Chlamydia trachomatis caused urinary reproductive system infections (urethritis and cervicitis); sensitive bacteria caused infection of skin soft tissue and other parts of the body; it can also used for non-specific and gonococcal genital infection, Legionella caused infection and Pediatric Infections.
Roxithromycin is characterized by acid resistance and excellent oral absorption with T1/2 being 12 to 14 hours which is 6 times higher than erythromycin. It has wide distribution in the body and is able to reach high concentration in both the upper and lower respiratory tract, reproductive tract and skin and maintain for a long time. Most of the metabolism occurs in vivo.
Roxithromycin clinical evaluation: the curing rate of chlamydia urethritis, cervicitis clinical and bacteriological was 93% to 97%; the efficacy against genital infection is similar to doxycycline; the cure rate for skin infection is 90% or more; the effectiveness for the treatment of respiratory infections is 83% and 50% while the effectiveness for the treatment of pneumonia and dental infections are 79% and 85%.
Production method
Take erythromycin as raw materials for reaction with hydroxylamine hydrochloride in triethylamine and methanol, generating oxime, followed by reaction with methoxy ethoxymethyl chloride in acetone to derive roxithromycin.
Antimicrobial activity
Activity against common pathogens is comparable to that of erythromycin. It is active against L. monocytogenes, C. jejuni, H. ducreyi, G. vaginalis, Bord. pertussis, C. diphtheriae, B. burgdorferi, H. pylori, the M. avium complex, Chlamydia spp., and U. urealyticum.
Pharmaceutical Applications
A semisynthetic derivative of erythromycin A formulated for oral use.
Pharmacokinetics
Oral absorption：50–55% Cmax 150 mg oral ： 7.9 mg/L after 1.9 h 300 mg oral ：10.8 mg/L after 1.5 hPlasma half-life ：10.5–11.9 hPlasma protein binding ：c. 90%absorption and metabolism Absorption is not affected by food. Oral administration with antacids or H2-receptor antagonists does not significantly affect bioavailability. In a direct comparison, the area under the time–concentration curve (AUC) produced by a 150 mg dose was 16 times greater than that produced by 250 mg erythromycin A. Behavior in children is broadly similar to that in adults, repeated doses of 2.5 mg/kg producing age-independent mean peak plasma concentrations around 10 mg/L at 1–2 h, but the apparent elimination half-life was longer (approximately 20 h). It is saturably bound to α-acid glycoprotein in plasma. The plasma clearance appears to be dose dependent or plasma concentration dependent.DistributionIt is widely distributed, but does not reach the CSF. Concentrations close to the simultaneous serum level have been found in tonsillar, lung, prostatic and other tissues. It achieves high levels in skin.DistributionIt is widely distributed, but does not reach the CSF. Concentrations close to the simultaneous serum level have been found in tonsillar, lung, prostatic and other tissues. It achieves high levels in skin.Metabolism and excretionLess than 5% of the administered dose is eliminated as degradation products. Rather more than half the dose appears in the feces and only 7–10% (including metabolites) in the urine： up to 15% is eliminated via the lungs. Renal clearance increased in volunteers as the dose was raised from 150 to 450 mg,
and is decreased in elderly subjects. In patients in whom the creatinine clearance was <10 mL/min, the apparent elimination half-life rose to around 15.5 h and total body clearance was significantly reduced. The apparent elimination half-life was somewhat increased in patients with hepatic cirrhosis.
Side effects
It is generally well tolerated, adverse effects being described in 3–4% of patients, mostly gastrointestinal disturbance (abdominal pain, nausea and diarrhea). Headache, weakness, dizziness, rash and reversible changes in liver function tests and increased eosinophils and platelets have also been described.
Check Digit Verification of cas no
The CAS Registry Mumber 80214-83-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,0,2,1 and 4 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 80214-83:
(7*8)+(6*0)+(5*2)+(4*1)+(3*4)+(2*8)+(1*3)=101
101 % 10 = 1
So 80214-83-1 is a valid CAS Registry Number.
InChI:InChI=1/C41H76N2O15/c1-15-29-41(10,49)34(45)24(4)31(42-53-21-52-17-16-50-13)22(2)19-39(8,48)36(58-38-32(44)28(43(11)12)18-23(3)54-38)25(5)33(26(6)37(47)56-29)57-30-20-40(9,51-14)35(46)27(7)55-30/h22-30,32-36,38,44-46,48-49H,15-21H2,1-14H3/t22-,23-,24+,25+,26-,27+,28+,29-,30+,32-,33+,34-,35+,36-,38+,39-,40-,41-/m1/s1
80214-83-1Relevant articles and documents
A process for the purification of roxithromycin
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Page 5, (2008/06/13)
A process for the purification of roxithromycin with high level of impurity -H comprising subjecting the impure roxithromycin to at least partial dissolution and/or suspension in solvent selected from ethanol, acetonitirle, aromatic solvents and mixture of ethanol and acetonitrile; followed by crystallizing to thereby obtain roxithromycin with desired level of impurity-H of less than 0.5%. The invention also relates to crystalline polymorphic forms B and C of roxithromycin obtained following the above process of purification and having impurity-H of less than 0.5%.
Process for preparing roxithromycin and derivatives thereof
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, (2008/06/13)
A process for preparing an erythromycin derivative of formula (1), such as roxithromycin, from the corresponding oxime is discloded. The oxime is reacted with a metal alkoxide and results in improvements over prior art processes involving the oxime. Roxithromycin is a known anti-bacterial agent.
