Disposition, pharmacokinetics, and metabolism of 14C-fotemustine in cancer patients.
The pharmacokinetics and metabolism of intravenously infused 14C-fotemustine (about 100 mg/m2) were examined in 2 cancer patients. Plasma levels of radioactivity increased to a maximum of 4.1 and 5.5 micrograms equivalents per g when the infusion stopped then declined triexponentially with mean half-lives of about 1/2, 10 and 80 h for the initial, mid and terminal phases, respectively. Plasma levels of intact drug were lower, with maximum levels of 1.1 and 2.8 micrograms/ml, and declined monophasically with a half-life of about 24 min. Plasma clearance was high (1426 and 764 ml/min) with the volume of distribution based on areas of 47.7 and 26.4 l. Most of the radioactivity was eliminated in urine (50.1 and 61.3%) over 7 days with smaller amounts in the feces (6.8 and 0.3%) and only minimal quantities (under 0.1%) as expired carbon dioxide. Metabolites of fotemustine were identified as chloroethanol and N-nitroso-1-imidazolone-ethyl-diethylphosphonate in plasma and as 1-hydantoin-ethyl-diethyl-phosphonate and acetic acid in urine.
Ings
R M
RM
Servier Research and Development Ltd., Fulmer, Slough, Bucks.
Gray
A J
AJ
Taylor
A R
AR
Gordon
B H
BH
Breen
M
M
Hiley
M
M
Brownsill
R
R
Marchant
N
N
Richards
R
R
Wallace
D
D
D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D005023:Ethylene Chlorohydrin / Q000097:blood; D005243:Feces / Q000737:chemistry; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013997:Time Factors
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D005023:Ethylene Chlorohydrin; C054368:fotemustine