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. The profile of 5-FU remained unaltered irrespective of the sequence of administration. However, following simultaneous administration of 5-FU and TCNU or pretreatment with 5-FU, plasma levels of TCNU were decreased by a factor of 2.5-3 as compared with those seen when TCNU was given alone. These decreased plasma levels were explained by an increase in the TCNU volume of distribution, although this was not due to alterations in TCNU plasma protein binding. These sequence-dependent alterations in the pharmacokinetic profile of TCNU correlate with and may explain previously reported differences in the anti-tumour activity and toxicity profile of this combination.
Hill
S R
SR
Clinical Oncology Unit, University of Bradford, W. Yorkshire, UK.
Bibby
M C
MC
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011485:Protein Binding; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
D001798:Blood Proteins; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea; D005472:Fluorouracil