ABSTRACT
4'-Deoxy-10,11,12,13-tetrahydrodesmycosin was prepared in six-step reactions. Antibacterial screening shows retained antibacterial spectrum of tylosin with some improvement against tylosin-sensitive Staphylococci and Haemophilus influenze. However, the pharmacokinetic data demonstrated rapid distribution from blood in tissues and prolonged maintenance in all tissues, especially in the lungs, in comparison with tylosin.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Tylosin/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Rats , Tissue Distribution , Tylosin/chemical synthesis , Tylosin/pharmacokinetics , Tylosin/pharmacologyABSTRACT
A series of the novel oleandomycin 9-oximes has been prepared and characterized by spectroscopic data and X-ray analysis. The antibacterial in vitro activities of the oximes (6-10) were compared with that of oleandomycin (1). Among the novel derivatives the most active compound was 8(R)-methyloleandomycin-9-oxime (9) in contrast ot its 8(S)-isomer (10) which possessed only low potency. Some preliminary pharmacokinetic data of 9 confirmed its activity. Compound 9 has been advanced to further biological study.
Subject(s)
Oleandomycin/chemistry , Oleandomycin/pharmacology , Animals , Bacteria/drug effects , Crystallography , In Vitro Techniques , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Oleandomycin/analogs & derivatives , Oleandomycin/pharmacokinetics , Rats , Tissue DistributionABSTRACT
A series of O-methylazithromycin derivatives have been synthesized and their antibacterial activities were compared with those of azithromycin (1). O-Methylation of 1 proceeded stepwise by the two main pathways beginning at the C-6 and C-11 hydroxyl groups, individually. Among O-methyl derivatives, 6-O-methylazithromycin A (11) was slightly less active than 1. The methylation of the secondary hydroxyl group at the C-11 position resulted surprisingly in an increase of their in vitro activity. The antibacterial activities of novel azalides decreased with increasing the number of the methyl groups introduced.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Erythromycin/analogs & derivatives , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Azithromycin , Erythromycin/chemical synthesis , Erythromycin/pharmacology , Magnetic Resonance Spectroscopy , Methylation , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
Azithromycin (CAS 83905-01-5) disks with the selected loading (10, 15, 20 micrograms) were used for determination of the most suitable azithromycin disk concentration. Estimation was carried out by means of the regression line related to the zone size inhibition. Testing was performed on a variety of freshly isolated gram-positive, gram-negative and anaerobic bacteria derived from various specimens collected from patients. Using the disk diffusion method with 10 micrograms of azithromycin per disk in total 431 gram-positive, 875 gram-negative bacterial strains and 59 anaerobic bacteria were analysed. It was concluded that azithromycin disk containing 10 micrograms is sufficient for determination of bacterial sensitivity.
Subject(s)
Bacteria/drug effects , Erythromycin/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Azithromycin , Bacteria, Anaerobic/drug effects , Bacterial Infections/microbiology , Erythromycin/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microbial Sensitivity TestsABSTRACT
Azithromycin, a macrolide antibiotic with an enhanced antimicrobial spectrum, was found to have a longer half-life than erythromycin, with marked tissue penetration. The pharmacokinetics of azithromycin after oral administration were compared with those of erythromycin in rats (200 mg kg-1) and rabbits (80 mg kg-1). Concentrations of azithromycin in liver, lung, kidney, ileum, and brain were higher than serum concentrations. The slow decline in tissue concentrations was evident from the biphasic elimination profile. Thus, advantageous pharmacokinetic properties and the broader antimicrobial spectrum of azithromycin relative to erythromycin appear to further support its therapeutic potential.
Subject(s)
Erythromycin/analogs & derivatives , Administration, Oral , Animals , Azithromycin , Erythromycin/administration & dosage , Erythromycin/blood , Erythromycin/pharmacokinetics , Female , Male , Rabbits , Rats , Rats, Inbred F344 , Tissue DistributionABSTRACT
An open, randomized, multicentre study compared the efficacy and safety of the prototype, azalide, azithromycin, and erythromycin in the treatment of atypical pneumonias. Azithromycin was administered for five days at a dosage of 250 mg bd on day 1 and 250 mg once daily on days 2 to 5. Erythromycin was given for ten days at 500 mg qid. Causative pathogens were identified by serological methods. Of 57 patients treated with azithromycin, Mycoplasma pneumoniae and Chlamydia psittaci were identified in 31 and eight patients, respectively. Of 44 patients treated with erythromycin, M. pneumoniae and C. psittaci were identified in 24 and eight patients, respectively. There were no therapeutic failures in either treatment group. Side effects were observed in one of 57 patients on azithromycin and in six of 44 patients on erythromycin. Azithromycin appears to be as effective as erythromycin in the treatment of atypical pneumonias and better tolerated.
