THERMODYNAMICS OF PARTITIONING OF THE ANTIMALARIAL DRUG MEFLOQUINE INPHOSPHOLIPID-BILAYERS AND BULK SOLVENTS

The antimalarial drug mefloquine binds avidly to phospholipids in biom embranes, The thermodynamics of the partitioning process in dimyristoy lphosphatidylcholine (DMPC) bilayers was investigated to give some ins ight into the drug-phospholipid interaction, Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium parti tion coefficients measured as a function of temperature, Negative valu es of Delta H and Delta S were obtained for the transfer of mefloquine from the aqueous to the gel phase of the phospholipid, The partitioni ng is enthalpy controlled which suggests that mefloquine interacts str ongly with the phospholipid phase, In contrast, the partitioning of me floquine into the liquid crystalline phase of DMPC is entropy controll ed which is typical of a hydrophobic interaction between mefloquine an d the aqueous phase. The partitioning of mefloquine into the bulk solv ents octanol and hexane were found to be enthalpy and entropy controll ed, respectively, The enthalpy dominated partitioning of mefloquine in to gel phase DMPC and octanol is attributed to the occurrence of hydro gen bonding and van der Waals interactions between solute and solvent, The flat shape of mefloquine may further aid its interaction with the orderly domains of the lipidic/organic phase, This is apparent from a comparison of the partitioning characteristics of another structurall y related but conformationally different molecule, quinine into DMPC a nd octanol.