Ml. Go et Tl. Ngiam, THERMODYNAMICS OF PARTITIONING OF THE ANTIMALARIAL DRUG MEFLOQUINE INPHOSPHOLIPID-BILAYERS AND BULK SOLVENTS, Chemical and Pharmaceutical Bulletin, 45(12), 1997, pp. 2055-2060
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.