Ther Drug Monit. 1995 Apr;17(2):179-83.
Quantitative determination of the antibiotic azithromycin [Zithromax] in human serum by high-performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry: correlation with a standard HPLC-electrochemical method.

Fouda HG, Schneider RP.

Central Research Division, Pfizer Inc., Groton, Connecticut 06340, USA.

A specific assay for the quantitative determination of the new antibiotic azithromycin [Zithromax] in a low volume of human serum is described. The assay uses on-line high-performance liquid chromatography (HPLC) and atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI). Deuterium-labeled azithromycin [Zithromax] was synthesized and used as the internal standard of the assay. The drug and the internal standard are extracted from 50 microliters of serum, and aliquots are injected onto a standard reverse-phase HPLC column. The effluent from the HPLC column at 1 ml/min is introduced into the atmospheric pressure source of a SCIEX API III mass spectrometer. Azithromycin [Zithromax] concentrations in serum are determined by the selected monitoring of the protonated molecular ions of the drug and the internal standard. Our assay yields accurate and precise results over the range 10 ng/ml to 250 ng/ml. The correlation between the assay and a standard HPLC-electrochemical method, requiring a larger volume of serum, has been determined. The two methods showed excellent agreement. Because of its low volume requirement, our HPLC-APCI assay can be substituted for the standard assay for the investigation of azithromycin [Zithromax] pharmacokinetics in children.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7624907&dopt=Abstract Zithromax azithromycin




Mutat Res. 1993 Jul;300(2):79-90.
Preclinical toxicology studies with azithromycin: genetic toxicology evaluation.

Amacher DE, Ellis JH Jr, Joyce AJ, Muehlbauer PA, Turner GN, Wahrenburg MG, Holden HE, Ray VA.

Central Research Division, Pfizer Inc., Groton, CT 06340.

Azithromycin [Zithromax] was subjected to a series of three in vitro and one in vivo genetic toxicology assays for the detection of drug-associated gene or chromosomal effects. In the Ames Salmonella typhimurium tester strains TA1535, TA1537, TA98 and TA100, the presence of azithromycin [Zithromax] was not associated with any increase in the number of his- revertants. Urine from mice dosed with up to 200 mg/kg of azithromycin [Zithromax] also had no effect on the number of revertants in these same strains suggesting the absence of mutagenic excretory products following oral exposure. When tested up to the cytotoxic level of 240 micrograms/ml, azithromycin [Zithromax] caused no increase in the mutant frequency at the thymidine kinase locus of L5178Y/TK cells. Both the mammalian and microbial gene mutation assays included the presence of rat-liver postmitochondrial (S9) fraction for the detection of mutagenic biotransformation products. Mitogen-stimulated human lymphocytes cultured in the presence of 2.5-7.5 micrograms/ml azithromycin [Zithromax] for 24 h or 30.0-40.0 micrograms/ml azithromycin [Zithromax] for 3 h in the presence of rat S9 had chromosomal aberration frequencies that were no different than negative control cells even though slight to moderate mitotic suppression was associated with these concentrations. In vivo assessment of this compound was completed in male and female mice with a single oral dose of 200 mg/kg followed by sacrifice at 6, 24 or 48 h later and metaphase analysis of bone marrow for chromosomal aberrations. No statistically significant elevations of chromosomally aberrant cells were found. We conclude that azithromycin [Zithromax] does not cause gene mutations in microbial or mammalian cells, or chromosomal aberrations in cultured human lymphocytes or in mouse bone marrow in vivo.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7685497&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1995 Jan;39(1):221-6.
Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin [Zithromax] on respiratory tract pathogens.

Odenholt-Tornqvist I, Lowdin E, Cars O.

Department of Infectious Diseases, University Hospital, Uppsala, Sweden.

Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics. In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin [Zithromax] on reference strains of Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae were investigated. The PAE was induced by 2x MICs (S. pneumoniae) or 10x MICs of the different drugs for 2 h, and the antibiotics were eliminated by washing and dilution. The PA SMEs were studied by addition of 0.1, 0.2, and 0.3x MICs during the postantibiotic phase of the bacteria, and the SMEs were studied by exposition of the bacteria to the drugs at the sub-MICs only. Growth curves were followed by viable counts for 24 h. The SMEs were generally very short. A PAE of 2.9 to 8 h was noted for all antibiotics against all strains. Clarithromycin induced a statistically significantly shorter PAE on S. pneumoniae than did roxithromycin and azithromycin [Zithromax] and did so also against H. influenzae in comparison with azithromycin. The PA SMEs were long and varied at 0.3x MIC between 6.4 19.6 h. This pronounced suppression of regrowth of bacteria which are first treated with a suprainhibitory concentration of antibiotics and then reexposed to sub-MIC levels indicates that long dosing intervals for macrolides and azalides can be allowed.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695310&dopt=Abstract Zithromax azithromycin




J Am Board Fam Pract. 1995 Jan-Feb;8(1):7-16.
Cost-effectiveness analysis of five different antibiotic regimens for the treatment of uncomplicated Chlamydia trachomatis cervicitis.

Nuovo J, Melnikow J, Paliescheskey M, King J, Mowers R.

Department of Family Practice, University of California, Davis 95817, USA.

BACKGROUND: The new Centers for Disease Control and Prevention treatment guidelines for Chlamydia trachomatis include two recently available drugs, azithromycin [Zithromax] and ofloxacin. The best choice for initial therapy remains controversial. OBJECTIVES: We wanted to perform a cost-effectiveness analysis of five different antibiotic regimens for the treatment of uncomplicated Chlamydia trachomatis cervicitis. METHODS: Using information gathered from a MEDLINE search of the English language literature from 1966 to 1994, employing the key words "cervicitis," "C. trachomatis," "erythromycin," "tetracycline," "doxycycline," "ofloxacin," and "azithromycin," we developed a decision analysis model specific for a nonpregnant woman with uncomplicated Chlamydia trachomatis cervicitis. Options in this model included an initially cured infection, a failed initial cure resulting in persistent cervicitis, or pelvic inflammatory disease treated either on an inpatient or outpatient basis. Probability estimates for each option were derived from previously published reports. A cost-effectiveness analysis was performed for three end points: cost per cure with initial therapy, cost per case of pelvic inflammatory disease averted, and cost per hospitalization averted. Sensitivity analyses were done by varying the cure rates for each antibiotic and the complication rates for failed therapy. The costs incurred for treatment were also varied. RESULTS: Using the high estimate for initial cure rates, doxycycline and tetracycline were the most cost-effective agents. Azithromycin [Zithromax] was the next most cost-effective agent, followed by ofloxacin and erythromycin. To achieve an equivalent final cost, the probability of initial cure with azithromycin [Zithromax] must exceed that of doxycycline by 3 percentage points. As the cost of azithromycin [Zithromax] decreases, the difference in initial cure rates between the two drugs to achieve an equivalent final cost becomes smaller. CONCLUSIONS: Doxycycline remains the drug of choice in the treatment of Chlamydia trachomatis cervicitis. The results favor the use of azithromycin [Zithromax] rather than doxycycline when there is concern for compliance to the standard doxycycline regimen. A lower cost for azithromycin [Zithromax] could favor its use as the drug of choice.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7701965&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1994 Nov;34(5):765-76.
Pharmacokinetics of azithromycin [Zithromax] and erythromycin in human endometrial epithelial cells and in cells infected with Chlamydia trachomatis.

Raulston JE.

Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599-7290.

The pharmacokinetics of azithromycin [Zithromax] and erythromycin were examined in uninfected and Chlamydia trachomatis infected human endometrial epithelial cells in vitro. Cells which were grown in a polarized orientation showed a three-fold higher quantity of azithromycin [Zithromax] uptake than did non-polarized cells. Cellular penetration profiles of azithromycin [Zithromax] exceeded erythromycin by as much as eight-fold. In addition, approximately 20% of azithromycin [Zithromax] remained cell-associated after 24 h in drug-free medium whereas erythromycin was not retained beyond 3 h. Hormone-responsive primary human endometrial gland epithelial cells, cultured directly after hysterectomy, showed enhanced uptake of both antimicrobials compared with laboratory adapted epithelial cell lines. Cells infected with a genital serovariant of C. trachomatis showed no significant difference in antibiotic uptake during the early stages of the chlamydial developmental cycle, and only a slight decrease in azithromycin [Zithromax] uptake in the late stage of infection compared with non-infected cells. Morphological evidence of the bactericidal activity of azithromycin [Zithromax] was evident in infected cells at most stages of the chlamydial developmental cycle, whereas the same concentration of erythromycin produced less evidence of marked bactericidal activity as observed by transmission electron microscopy.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7706172&dopt=Abstract Zithromax azithromycin

smh.toronto.on.ca

There is increasing data implicating Chlamydia pneumoniae in the pathogenesis of atherosclerosis, and antibiotics may theoretically be useful to prevent secondary vascular complications. Three groups of New Zealand White specific-pathogen-free rabbits, fed cholesterol-free chow, were inoculated via the nasopharynx on three occasions, 2 weeks apart, with C. pneumoniae. Group I (n = 23) rabbits were untreated; group II (n = 24) rabbits were treated with azithromycin [Zithromax] at 30 mg/kg of body weight daily for 3 days and then once every 6 days, starting 5 days after first inoculation and continuing until sacrifice (early treatment); and group III (n = 24) rabbits were treated with the same dose of azithromycin [Zithromax] but initiated 2 weeks after the last inoculation. All animals were sacrificed at 10 to 11 weeks after initial inoculation and examined for signs of atherosclerosis of the aorta. Eight (34.8%) untreated rabbits developed early signs of atherosclerosis, whereas only one (4.2%) in the early-treatment group had such signs (P = 0.02). However, eight rabbits (33.3%) of the delayed-treatment group had atherosclerotic changes of the aorta and no significant reduction compared to untreated rabbits. Early treatment of C. pneumoniae-infected rabbits with azithromycin [Zithromax] was highly effective (87%) in preventing atherosclerotic changes, but delayed treatment was ineffective. It is possible that longer or more aggressive antibiotic treatment may be needed to reverse preformed lesions or that antibiotics may not be of value once lesions have formed.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10548582&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1994 Dec;34(6):989-99.
The effect of a single oral dose of azithromycin [Zithromax] on chlamydial infertility and oviduct ultrastructure in mice.

Tuffrey M, Woods C, Inman C, Ward M.

Department of Microbiology, St Marys Hospital Medical School, London, UK.

Azithromycin [Zithromax] has been recommended for the treatment of human chlamydial genital tract infections because of the sustained, chlamydicidal levels of the antibiotic which can be achieved after a single dose. The effect of single dose azithromycin [Zithromax] on the prevention or reversal of chlamydial-induced damage to the oviduct or to fertility was assessed in a mouse model of chlamydial salpingitis which closely mimics the human disease. C3H mice were treated with progesterone and then inoculated under the ovarian bursa with a human genital tract isolate of Chlamydia trachomatis, serovar F. Azithromycin [Zithromax] at doses from 135-250 mg/kg was administered by oral intubation. Morphological damage to the oviduct lumen was assessed by scanning electron microscopy, while fertility was assessed by breeding experiments. Treatment of mice two or seven days after infection with 135 mg/kg azithromycin [Zithromax] completely reversed chlamydial-induced ultrastructural changes and infertility. Treatment 12 or more days after infection, at doses as high as 250 mg/kg, failed to prevent infertility. The onset of fertility correlated with the loss of ciliated epithelia from the oviduct. However, the regeneration of ciliated epithelia following azithromycin [Zithromax] treatment did not necessarily restore tubal patency. These results, if true for women also, indicate the need for rapid, effective antibiotic therapy for chlamydial salpingitis to prevent infertility and other sequelae of tubal damage.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7730241&dopt=Abstract Zithromax azithromycin