Effects of routes of administration of TCNU on its plasma, tissue and tumour concentrations.
Tissue and plasma samples were taken from normal and tumour bearing mice at various time intervals following a dose of 30 mg kg-1 TCNU given by various routes. TCNU levels were measured by HPLC. The results show that the route of administration influences plasma concentrations, bioavailability and tissue and tumour concentrations. Intravenous administration gave 100% plasma bioavailability but only 15% of this level was seen following oral administration with consequently lower levels in tissues and tumours. The effect of gastric contents played a major role in this reduced bioavailability and plasma levels increased to 65% following overnight fasting. The differences in concentrations of TCNU observed here in plasma, tumour and normal tissues after oral and intravenous administration may have important clinical implications and may influence both anti-tumour activity and toxicity.
Double
J A
JA
Clinical Oncology Unit, University of Bradford, West Yorkshire, U.K.
Bibby
M C
MC
Loadman
P M
PM
Bloomer
J C
JC
D000230:Adenocarcinoma / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D003110:Colonic Neoplasms / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009607:Nitrosourea Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea