engleski

Peculiar pharmacokinetics of macrolides. The role of membrane potential

Macrolides consist of a large macrolactone ring of different sizes with several sugar substituents, usually L-cladinose and D-desosamine, attached to it. Since identification and isolation of the erythromycin, first macrolide compound with 14-membered ring, a lot of research efforts have been made to chemically modify it in order to eliminate its adverse effect and to improve its pharmacological profile. Presently, macrolides have diversified into many different directions with varying ring sizes and different chemical structures. Azithromycin, the first 15-membered macrolide compound synthesized in PLIVA laboratories, has one additional nitrogen incorporated into the macrolactone ring which, together with tertiary amine on desosamine sugar moiety, gives it dibasic properties. Azithromycin possesses similar activity profile against Gram-positive and improved activity against Gram-negative bacteria comparing to erythromycin. However, it stands out among other macrolide antibiotics due to its extraordinary pharmacokinetics resulting in a significantly lower administration doses. Although very high accumulation of azithromycin in polymorphonuclear neutrofiles (PMN) in vivo was found, the reason for such interesting behavior is still not explained. The question still remains whether the transport of macrolides through the biological membranes is passive or active. It seems reasonable to assume that the different states of membranes and not macrolides themselves are responsible for such behavior. In this presentation the results on the electrochemical transfer potentials of macrolides across liquid/liquid interface will be described and correlated with pharmacological data on uptake of different macrolides in PMNs.

macrolides, pharmacokinetics, membrane potential, cyclic voltammetry

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