Time and Concentration Dependent Influence of Dirithromycin on Neutrophils Oxidative Burst

H. LEVERT; B. GRESSIER; C. BRUNET; T. DINE; M. LUYCKX; L. BALLESTER; F. TEMPLIER; M. CAZIN; J. C. CAZIN

doi:10.7164/antibiotics.52.127

H. LEVERT, B. GRESSIER, C. BRUNET, T. DINE, M. LUYCKX, L. BALLESTER, F. TEMPLIER, M. CAZIN, J. C. CAZIN

Author information

H. LEVERT
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
B. GRESSIER
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
Laboratoire de Biologic, Centre hospitalier d'Armentieres, rue S. Carnot
C. BRUNET
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
T. DINE
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
M. LUYCKX
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
L. BALLESTER
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
F. TEMPLIER
Laboratoire de Biologic, Centre hospitalier d'Armentieres, rue S. Carnot
M. CAZIN
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques
J. C. CAZIN
Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques

JOURNAL FREE ACCESS

1999 Volume 52 Issue 2 Pages 127-133

DOI https://doi.org/10.7164/antibiotics.52.127

Details

Abstract

Dirithromycin is a 14-membered macrolide antibiotic, well known to yield high intragranulocytic levels after several hour exposure. We chose therefore to investigate oxidative metabolism after prolonged incubation periods with neutrophils.
Neutrophil generation of reactive oxygen species, represented by superoxide anion, was assessed after fMLP or Staphylocoecus aureus-induced activation of the respiratory burst. Cellular uptake of the drug was assessed concurrently, in order to attempt a correlation with time-dependent modifications of the cellular oxidative status.
For 1 hour exposure time, a pro-oxidant effect was reported for lower concentrations, achievable during therapeutic administration, whereas the highest ones promoted a potent anti-oxidant effect. After prolonged incubation times, the anti-oxidant effect alone was reported, with time-dependent modifications of IC₅₀ values. These values could be correlated with intracellular accumulation of the drug. The anti-inflammatory activity reported here for high dirithromycin concentrations, could be nevertheless clinically relevant, since dirithromycin cellular uptake extends beyond 4 hours.

Corresponding author

Register with J-STAGE for free!