J Antimicrob Chemother. 1993 Jun;31 Suppl E:57-63.
Pharmacokinetics of azithromycin [Zithromax] in patients with impaired hepatic function.

Mazzei T, Surrenti C, Novelli A, Crispo A, Fallani S, Carla V, Surrenti E, Periti P.

Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.

The pharmacokinetics of azithromycin [Zithromax] were determined over a 192-h period following oral administration of a single 500-mg dose to six healthy volunteers and to 16 cirrhotic patients (ten class A and six class B; Pugh's classification). Plasma and urinary levels were determined by microbiological assay. The mean Cmax, obtained 2-3 h after administration, was 0.29 mg/L in volunteers, and 0.39 and 0.51 mg/L in class A and class B cirrhosis, respectively. The elimination half-life was 53.5 h in control subjects, and 60.6 and 68.1 h in class A and class B cirrhotic patients, respectively. The mean residence time was significantly higher in class B patients, but AUC, Vd, Cltot and Clr values appeared to be similar in all groups. The mean urinary recovery of azithromycin [Zithromax] at 192 h varied from 11-15.7%, and did not differ significantly among groups. These results demonstrate that azithromycin [Zithromax] pharmacokinetics do not differ consistently in patients with mild or moderate hepatic impairment in comparison with healthy volunteers. Therefore, no dosage modifications of azithromycin [Zithromax] seem to be required for patients with class A or B liver cirrhosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396098&dopt=Abstract Zithromax azithromycin




J Chemother. 1993 Jun;5(3):155-8.
In vitro activity of azithromycin [Zithromax] against Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis in comparison with erythromycin, roxithromycin and minocycline.

Rumpianesi F, Morandotti G, Sperning R, Satta G, Cevenini R.

Institute of Microbiology, University of Bologna, Italy.

The in vitro activity of azithromycin [Zithromax] against 40 strains of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis was investigated in comparison with erythromycin, roxithromycin and minocycline. All C. trachomatis strains were inhibited by azithromycin [Zithromax] at a concentration < or = 0.5 microgram/ml. The initial minimum inhibitory concentration (MIC) of the drug for U. urealyticum was 4 microgram/ml, whereas some resistance against the drug was shown by M. hominis. Erythromycin and roxithromycin presented almost comparable activities, whereas minocycline was slightly more active than macrolides against C. trachomatis (MIC < or = 0.25) and more active against M. hominis (initial MIC < or = 1 micrograms/ml). Only 97% of U. urealyticum strains were susceptible to 8 micrograms/ml of minocycline.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8396626&dopt=Abstract Zithromax azithromycin




Ginecol Obstet Mex. 1993 Sep;61:261-4.
[Efficacy and safety of azithromycin [Zithromax] in the treatment of female genital Chlamydia trachomatis infections]

[Article in Spanish]

Narcio Reyes LE, Casanova Roman G, Arredondo Garcia JL.

Departamento de Infectologia e Inmunologia, Instituto Nacional de Perinatologia, Mexico, D.F.

Genital tract infections by Chlamydia trachomatis associated to sterility and infertility problems as well as perinatal complications have become increasingly frequent. Azithromycin [Zithromax] is a new macrolide with a lower activity spectrum than erythromycin and a longer half life as well as less secondary effects. The objective of the study was to evaluate the safety and efficiency of Azithromycin [Zithromax] on genital tract infection by C. trachomatis. MATERIAL AND METHODOLOGY. A total of 30 nonpregnant women between the ages of 19 and 35 were studied; 70% had only one sexual partner. In order to insure the presence of C. trachomatis as unique pathogen, cervicovaginal sampling, clinical evaluation and gynecologic exploration were undertaken. One dose of 1 g orally of Azithromycin [Zithromax] was administered evaluating microbiologic and clinical remission at days 7-10, 12-16 and 33-37 after treatment. RESULTS. Two patients abandoned the study; global criteria of the evaluation were good to excellent in 17 cases; moderate to sufficient in six and poor in five. None of the cases reported secondary reactions. Results showed that Azithromycin [Zithromax] treatment of cervicitis by C. trachomatis is useful with the advantage of unique dose administration.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8406112&dopt=Abstract Zithromax azithromycin




J Antimicrob Chemother. 1995 Jul;36(1):215-8.
In-vitro activity of a new quinolone (CP-99,219) compared with ciprofloxacin, pefloxacin, azithromycin [Zithromax] and penicillin against Neisseria gonorrhoeae.

van Rijsoort-Vos JH, Stolz E, Verbrugh HA, Kluytmans JA.

Department of Clinical Microbiology, University Hospital, Rotterdam, The Netherlands.

The in-vitro activities of CP-99, 219, ciprofloxacin, pefloxacin, azithromycin [Zithromax] and penicillin was tested against 114 Neisseria gonorrhoeae strains. The MIC90s were: 0.008 mg/L (MIC range 0.001-0.06 mg/L) for CP-99, 219, 0.008 mg/L (MIC range 0.001-0.25 mg/L) for ciprofloxacin, 0.12 mg/L (MIC range 0.008-4 mg/L) for pefloxacin, 0.25 mg/L (MIC range 0.03-1 mg/L) for azithromycin [Zithromax] and 16 mg/L (MIC range 0.015-16 mg/L) for penicillin. The activity of CP-99,219 against various N. gonorrhoeae isolates was comparable to ciprofloxacin.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8537268&dopt=Abstract Zithromax azithromycin




Pathol Biol (Paris). 1995 Jun;43(6):512-4.
Azithromycin [Zithromax] drug interactions.

Felstead S.

Clinical and Safety Regulatory Affairs, PFYZER Central Research, Sandwich, UK.

Pre clinical work in vivo and in vitro have suggested that azithromycin [Zithromax] has a low potential for significant drug interactions. Clinical studies conducted thus far have generated results in accordance with the preclinical science [6]. Direct comparisons with the most modern macrolides have been published and evidence suggests that azithromycin [Zithromax] is likely to be associated with fewer significant drug interactions. However, as a final point, I wish to point out that proof of an absolute negative is not possible and therefore in any patient, on multiple medication with adverse findings, a drug interaction should be considered as part of the differential diagnosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8539073&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1995 Sep;39(9):1938-47.
In vivo efficacy of azithromycin [Zithromax] in treatment of systemic infection and septic arthritis induced by type IV group B Streptococcus strains in mice: comparative study with erythromycin and penicillin G.

Tissi L, von Hunolstein C, Mosci P, Campanelli C, Bistoni F, Orefici G.

Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.

We compared the activities of azithromycin, erythromycin, and penicillin G in a mouse model of systemic infection and septic arthritis induced by type IV group B streptococci (GBS). The in vitro and in vivo efficacy data for these drugs were analyzed relative to the pharmacokinetics of the drugs in sera, joints, and kidneys. Adult CD-1 mice were infected intravenously with 10(7) CFU of type IV GBS. Intraperitoneal drug administration was initiated with different dose regimens at different times after infection. A single dose of azithromycin [Zithromax] (100 mg/kg) strongly reduced the incidence of articular lesions with respect to that with erythromycin or penicillin G. Treatment with azithromycin [Zithromax] (three intraperitoneal administrations of 50 mg/kg at 12-h intervals) resulted in the complete prevention of arthritis. In contrast, erythromycin was poorly effective and penicillin G was effective only if inoculated 30 min after infection and at high doses (400,000 or 600,000 IU/kg). Furthermore, azithromycin [Zithromax] was able to cure about 70% of the mice when administered 7, 8, and 9 days after GBS infection. Azithromycin [Zithromax] was much more active than erythromycin and penicillin G with respect to bacterial killing in the joints and kidneys. In fact, cultures from these tissues were always negative no matter what treatment schedule was employed. The pharmacokinetics of azithromycin [Zithromax] account for its superior in vivo efficacy against type IV GBS. A longer half-life and higher levels of this drug in serum and tissues with respect to those for erythromycin or penicillin G were achieved. The high affinity of azithromycin [Zithromax] for the joints strongly supports its potential value for therapy of septic arthritis, which is a severe and frequent clinical manifestation of GBS infection.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540695&dopt=Abstract Zithromax azithromycin




Antimicrob Agents Chemother. 1995 Sep;39(9):2104-11.
Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection.

Oh YK, Nix DE, Straubinger RM.

Department of Pharmaceutics, University at Buffalo, State University of New York, Amherst 14260-1200, USA.

Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial system. Current therapy is not highly effective. Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more efficiently to M. avium-infected cells. We investigated the formulation of the antibiotics ciprofloxacin and azithromycin [Zithromax] in liposomes and tested their antibacterial activities in vitro against M. avium residing within J774, a murine macrophage-like cell line. A conventional passive-entrapment method yielded an encapsulation efficiency of 9% for ciprofloxacin and because of aggregation mediated by the cationic drug, was useful only with liposomes containing < or = 50 mol% negatively charged phospholipid. In contrast, ciprofloxacin was encapsulated with > 90% efficiency, regardless of the content of negatively charged lipids, by a remote-loading technique that utilized both pH and potential gradients to drive drug into preformed liposomes. Both the cellular accumulation and the antimycobacterial activity of ciprofloxacin increased in proportion to the liposome negative charge; the maximal enhancement of potency was 43-fold in liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5). Azithromycin [Zithromax] liposomes were prepared as a freeze-dried preparation to avoid chemical instability during storage, and drug could be incorporated at 33 mol% (with respect to phospholipid). Azithromycin [Zithromax] also showed enhanced antimycobacterial effect in liposomes, and the potency increased in parallel to the moles percent of negatively charged lipids; azithromycin [Zithromax] in DSPG-Chol (10:5) liposomes inhibited intracellular M. avium growth 41-fold more effectively than did free azithromycin. Thus, ciprofloxacin or azithromycin [Zithromax] encapsulated in stable liposomes having substantial negative surface charge is superior to nonencapsulated drug in inhibition of M.avium growth within cultured macrophages and may provide more effective therapy of M.avium infections.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8540724&dopt=Abstract Zithromax azithromycin