Thermodynamics Of Fluoxetine Partitioning Into Lipid Membranes

Abstract

The partition coefficients (Kp) of fluoxetine, a well prescribed SSRI antidepressant between saturated neutral charge 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), saturated negative charge 1,2-dipalmitoyl-sn-glycero-3- phosphoglycerol (DPPG) large unilamellar vesicles (LUV 100 nm) and water were determined over the temperature range of 25 -37 by using the second derivative spectrophotometric method. The van’t Hoff analysis of the temperature dependence of Kp value revealed the positive =H and positive =S suggesting an entropy driven mechanism for fluoxetine partitioning into DPPC and DPPG lipid bilayers. Fluoxetine was found to have an increase in the partition coefficient with increasing temperature in two kind of lipids used in this study. The partition coefficient of fluoxetine into DPPG is higher than into DPPC suggesting the positively charged drug molecules are highly accessible to the negative charge DPPG. An in-depth study of the thermodynamic characterization of fluoxetine can shed light onto understanding the energetic forces driving binding interactions and it essential for understanding and optimizing molecular interactions of fluoxetine into lipid membranes, that is important key for drug design. Keywords: Fluoxetine, DPPG, DPPC Thermodynamics Partitioning Van’t Hoff method Second derivative spectrophotometer 1