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In order to evaluate the arrhythmogenic potency of macrolide antibiotics in a quantitative manner, we analyzed the influence of clarithromycin (CAM), roxithromycin (RXM), and azithromycin (AZM) on Q-T intervals from pharmacokinetic and pharmacodynamic points of view and in comparison with the potency of erythromycin (EM) previously reported by us for rats. Male Sprague-Dawley rats were anesthetized, and CAM (6.6, 21.6, and 43.2 mg/kg of body weight/h), RXM (20 and 40 mg/kg/h), and AZM (40 and 100 mg/kg/h) were intravenously injected for 90 min to obtain the time courses of drug concentrations in plasma and the changes in the Q-T intervals during and after the drug injections. Distinct Q-T interval prolongation of up to 10 ms was observed with CAM at its clinical concentrations. RXM and AZM evoked Q-T interval prolongation at concentrations higher than their clinical ranges. The potencies for Q-T interval prolongation, assessed as the slope of the concentration-response relationship, were 6.09, 0.536, and 0.989 ms. ml/microg for CAM, RXM, and AZM, respectively. There was hysteresis between the change in the Q-T intervals and the time course of the plasma concentration of each drug. The rank order of clinical arrhythmogenicity was estimated to be EM > CAM > RXM > AZM, as assessed from the present results and our previous report for EM. In conclusion, RXM and AZM were estimated to be less potent at provoking arrhythmia than EM and CAM. These results should be useful for making a safer choice of an appropriate agent for patients with electrocardiographic risk factors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10991836&dopt=Abstract
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Pharmacotherapy. 2000 Sep;20(9):1055-9.
Retrospective evaluation of a potential interaction between azithromycine and warfarin in patients stabilized on warfarin.
Beckey NP, Parra D, Colon A.
Department of Veterans Affairs Medical Center, West Palm Beach, Florida 33410, USA.
STUDY OBJECTIVE: To investigate a potential interaction between azithromycin and warfarin. DESIGN: Retrospective case-control study. SETTING: Veterans Affairs medical center. PATIENTS: Fifty-two patients stable on anticoagulation therapy. INTERVENTION: Patients who received a prescription for azithromycin and warfarin at any time since the hospital was opened, June 1, 1995, to July 22, 1999, were identified through a computerized report generated from the pharmacy prescription package. MEASUREMENTS AND MAIN RESULTS: Patients having a stable international normalized ratio (INR; defined as a therapeutic INR +/- 0.2) for at least two consecutive visits before receiving an azithromycin prescription were reviewed. Changes in INR from before and after addition of azithromycin were compared with changes in a control group. Controls were identified from a computer-generated report of patients who received a prescription for terazosin and warfarin at any time since the hospital was opened to July 22, 1999 (terazosin was chosen as it has no known interaction with warfarin). These patients also had a stable INR for at least two consecutive visits before receiving the terazosin prescription. In patients with INRs on record within 14 days after starting azithromycin or terazosin (9 patients/group), the average change in INR was 0.18 +/- 0.48 in the azithromycin group and 0.07 +/- 0.49 in the terazosin group (p=0.60). For patients with an INR on record within 30 days after starting azithromycin or terazosin (26 patients/group), the average change in INR was 0.25 +/- 0.67 in the azithromycin group and 0.05 +/- 0.55 in the terazosin group (p=0.18). CONCLUSION: An interaction between azithromycin and warfarin was not observed in this retrospective review of patients with a stable INR receiving the combination.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10999497&dopt=Abstract
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MMWR Morb Mortal Wkly Rep. 2000 Sep 22;49(37):833-7.
Fluoroquinolone-resistance in Neisseria gonorrhoeae, Hawaii, 1999, and decreased susceptibility to azithromycin in N. gonorrhoeae, Missouri, 1999.
[No authors listed]
In 1999, 360,076 cases of gonorrhea were reported in the United States (1). Gonorrhea is a major cause of pelvic inflammatory disease, often leading to ectopic pregnancy and infertility, and it can facilitate human immunodeficiency virus (HIV) transmission (2). During the 1980s, resistance to penicillin and tetracycline among gonococcal isolates became widespread; as a result, CDC recommended that other antimicrobial agents be used to treat gonorrhea. This report summarizes investigations of an increase in fluoroquinolone-resistant Neisseria gonorrhoeae in Hawaii and of a cluster of N. gonorrhoeae infections with decreased susceptibility to azithromycin in Missouri.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11012233&dopt=Abstract
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