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Assessment of Macrolide Transport Using PAMPA, Caco-2 and MDCKII-hMDR1 Assays

Danijela Nožinić ; GlaxoSmithKline Research Centre Zagreb, Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia
Astrid Milić ; GlaxoSmithKline Research Centre Zagreb, Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia
Lara Mikac ; Division of Materials Physics, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia
Jovica Ralić ; GlaxoSmithKline Research Centre Zagreb, Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia
Jasna Padovan ; GlaxoSmithKline Research Centre Zagreb, Ltd., Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia
Roberto Antolović ; Department of Biotechnology, University of Rijeka, S. Krautzeka bb, 51000 Rijeka, Croatia

Sažetak

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.

Ključne riječi

macrolides; permeability; P-glycoprotein; PAMPA; Caco-2; MDCK

Hrčak ID:

62210

URI

https://hrcak.srce.hr/62210

Datum izdavanja:

5.10.2010.

Posjeta: 3.984 *