Jones H E, Blundell G K, Wyatt I, John R A, Farr S J, Richards R J
Welsh School of Pharmacy, University of Wales College of Cardiff, U.K.
Biochem Pharmacol. 1992 Feb 4;43(3):431-7. doi: 10.1016/0006-2952(92)90560-6.
The aromatic diamidine, pentamidine, accumulated into rat lung slices by an uptake system that obeyed saturation kinetics, with an average Km value of 554 microM and a Vmax value of 4077 nmol/g lung wet wt/30 min, respectively. This system was not inhibited by metabolic inhibitors but was greatly diminished by lowering the temperature from 37 degrees to 4 degrees. Both compounds, pentamidine and putrescine, inhibited the uptake of the other and the inhibition of pentamidine accumulation by putrescine was demonstrated to be non-competitive. Uptake of putrescine was inhibited by increasing concentrations of pentamidine. As putrescine accumulates in epithelial type 1 and type 2 cells and in Clara cells, it is likely that pentamidine is also accumulated in these cell types but does not utilize the pulmonary uptake system for polyamine transport. Within the time period studied, toxic effects of the drug were not observed.
