Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo.

Antimicrobial Agents and Chemotherapy
J G den HollanderF Espersen

Abstract

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. Howev...Continue Reading

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Citations

Apr 18, 2002·Antimicrobial Agents and Chemotherapy·Pamela R TessierDavid P Nicolau
Jul 20, 2002·The Lancet Infectious Diseases·Javier Garau
Feb 19, 2009·Antimicrobial Agents and Chemotherapy·Anne SandbergNiels Frimodt-Møller
Jan 5, 2002·American Journal of Veterinary Research·S JacksK A Merritt
Nov 30, 2007·Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine·A GoudahA M Abd El-Aty
Jan 26, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Joseph P Lynch III, Fernando J Martinez
Feb 14, 2003·Journal of Chemotherapy·A NovelliT Mazzei
Aug 11, 2004·American Journal of Clinical Dermatology·Iain B Gosbell
Nov 16, 2006·The Journal of Antimicrobial Chemotherapy·Camilla Wiuff, Dan I Andersson
Jan 16, 2007·Journal of Veterinary Pharmacology and Therapeutics·L AmbrosM I San Andres
Sep 13, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·J J Schentag
Nov 30, 2002·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Antonello Di PaoloMario Del Tacca
Jan 17, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Carlos Bantar
Feb 5, 2004·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M R Jacobs
Sep 14, 2004·American Journal of Respiratory and Critical Care Medicine·Wan C TsaiTheodore J Standiford

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