Uptake of doxifluridine by rabbit small intestinal brush-border membrane vesicles.
Characteristics of the transport of doxifluridine (5'-DFUR) in rabbit small intestinal brush-border membrane vesicles were examined. 5'-DFUR was rapidly incorporated and a linear relation was found between the concentration of 5'-DFUR and its uptake rate in the concentration range tested (0.1-10 mM). The uptake rate increased at an acidic pH, at which 5'-DFUR is present mostly in an undissociated form. However, the uptake rate was not changed either by the extravesicular Na+ concentration or by the inside negative membrane potential. Nucleosides, uridine and adenosine only slightly inhibited the uptake, even at a fifty-fold concentration, and nucleobases, uracil and thymine had no effect. These results suggest the possibility of the major involvement of passive diffusion of the undissocated form of 5'-DFUR in the uptake of the drug through the brush-border membrane at a relatively high concentration.
Kitagawa
S
S
Niigata College of Pharmacy, Japan.
Hasegawa
M
M
Sato
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D005467:Floxuridine / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits
D000970:Antineoplastic Agents; D005467:Floxuridine; C025034:doxifluridine