3 research outputs found
Assessment of Macrolide Transport Using PAMPA, Caco-2 and MDCKII-hMDR1 Assays
The transport of commercially available macrolide antibiotics erythromycin, clarithromycin,
roxithromycin, azithromycin, and telithromycin was studied by PAMPA, a model of passive diffusion,
and by two models of active transport, Caco-2 and MDCKII-hMDR1. An involvement of efflux pump
P-glycoprotein (P-gp) in macrolide transport was also examined. Generally, in Caco-2 and MDCKII-hMDR1
assays without P-gp inhibition, a significantly lower apparent permeability (Papp) in apical-to-basolateral
(AB) than basolateral-to-apical (BA) direction was observed [efflux ratio, Pappratio(BA/AB) > 4.2]. Upon
P-gp inhibition, Papp(AB) was increased and Papp(BA) was decreased. The observed Papp values, their
efflux ratios, as well as a significant decrease in efflux ratios caused by P-gp inhibition (> 50 %) qualify
all tested macrolides as P-gp substrates. Results obtained with PAMPA suggest that this assay is not a method
of choice for screening of macrolide permeability due to the lack of P-gp efflux pump and/or other
transporters potentially involved in macrolide transport
Macrolactonolides: a novel class of anti-inflammatory compounds
A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described