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STUDY OF THE INFLUENCE OF BILE SALTS AND LECITHIN ON DISTRIBUTION OF KETOCONAZOLE BETWEEN PLASMA AND METHYLENE CHLORIDE

GABRIELA PAHOMI¹, GHEORGHE CORLAN¹, VALENTINA ANUTA¹, ROXANA SANDULOVICI¹, IONUŢ MIRCIOIU²

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The aim of the paper was to estimate the effect of increased amounts of bile salts and lecithin following postprandial changes in human plasma composition on the liquid/liquid extraction of a hydrophobic moiety. The effect could be integrated in what is called “matrix food effect”. Experiments concerned separation from plasma samples in methylene chloride by liquid/liquid extraction of the lipophilic drug ketoconazole (K) in presence of various amounts of sodium taurocholate bile salt (BS), lecithin (L) or their mixture. Determinations were performed at three concentration levels within the therapeutic range of ketoconazole. The use of L increased the extraction yield of K from plasma. The effect of L on K extraction was not linear but rather parabolic: a significant increase occurred in the L concentration range 1-10 mg/mL and a return towards initial values in the 10-50 mg/mL domain. The effect of BS on K extraction appeared to be rather fluctuant. At high analyte concentrations, the dependence BS concentration-K extraction yield was found to also be parabolic, but the effect was smoother than in the case of L. The enrichment of plasma with both BS and L led to a similar behaviour to L, a parabolic evolution of K extraction as a function of BS+L mixture concentration being obtained. The addition of BS+L mixture led to an enhanced response over both the effect of L and the sum of separate effects of BS and L. The maximum effect corresponded to lowrange concentrations of BS and L.