Computer-aided prediction of macrolide antibiotic concentrations in human circulating polymorphonuclear leucocytes.
Bouvier d'Yvoire MJ, Dresco IA, Tulkens PM
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.
PMID: 9579715, UI: 98239318