TEMPERATURE-DEPENDENCE OF MELPHALAN EFFLUX KINETICS IN CHINESE-HAMSTER OVARY CELLS

The temperature dependence of the kinetics of efflux of melphalan from Chinese hamster ovary (CHO) cells was studied from 4-degrees to 47-degrees. Time courses for melphalan efflux showed an initial rapid phase of efflux followed by a plateau. The data for melphalan concentration (c) versus efflux time (t) were described by the equation c(t) = A + B exp(-kt), where A is the final steady-state melphalan concentrations, B is the total change in melphalan concentration from time zero until steady-state conditions are reached, and k is the rate constant for the efflux process. The plateau level obtained was not dependent on temperature and corresponded to 22 +/- 3.2% of the drug remaining in the cells after efflux. The time for melphalan efflux to reach the plateau level was dependent on temperature. This was reflected by an increase in the rate constants for melphalan efflux with increasing temperature from 30-degrees to 47-degrees. The rate constant for melphalan efflux at 37-degrees was 0.045 +/- 0.002 min-1. Efflux of melphalan occurred much more slowly at lower temperatures such as 4-degrees and 20-degrees. An Arrhenius plot for melphalan efflux showed a linear and decreasing trend at temperatures between 30-degrees and 47-degrees with an activation energy of 1.046 x 10(3) J/mol.