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Journal of Antimicrobial Chemotherapy, Vol 41, 63-68, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy

ORIGINAL ARTICLES

Computer-aided prediction of macrolide antibiotic concentrations in human circulating polymorphonuclear leucocytes

MJ Bouvier d'Yvoire, IA Dresco and PM Tulkens
Hoechst Marion Roussel Medical Development, Paris, France.

The relative in-vivo intracellular concentration of various macrolides in phagocytes cannot be directly extrapolated from in-vitro experiments that use a fixed and constant extracellular concentration for all compounds, since this fails to consider different rates of intracellular penetration, dosage regimens and pharmacokinetic data. In the proposed model, which takes into account the free plasma concentrations and accumulation characteristics of three antibiotics, roxithromycin, azithromycin and erythromycin, we show that roxithromycin and azithromycin may reach similar concentrations in human polymorphonuclear leucocytes when conditions mimic clinical administration of these drugs, while erythromycin concentrations are lower. This approach may be useful to predict the behaviour of other drugs or other cells, and to assist in the design of rational treatment schemes.
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