5-FLUOROURACIL CAUSES ALTERATIONS IN THE PHARMACOKINETIC PROFILE OF TAUROMUSTINE IN NMRI MICE

The pharmacokinetic profiles of 5-fluorouracil (5-FU) and tauromustine (TCNU) were investigated in NMRI mice following their administration either alone or as part of simultaneous or sequential combinations. Th e profile of 5-FU remained unaltered irrespective of the sequence of a dministration. However, following simultaneous administration of 5-FU and TCNU or pretreatment with 5-FU, plasma levels of TCNU were decreas ed by a factor of 2.5-3 as compared with those seen when TCNU was give n alone. These decreased plasma levels were explained by an increase i n the TCNU volume of distribution, although this was not due to altera tions in TCNU plasma protein binding. These sequence-dependent alterat ions in the pharmacokinetic profile of TCNU correlate with and may exp lain previously reported differences in the antitumour activity and to xicity profile of this combination.