Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i.v. bolus administration of thio-TEPA in ovarian cancer patients.
The serum pharmacokinetics of unchanged thio-TEPA and the active metabolite TEPA and the urinary excretion of thio-TEPA, TEPA and total alkylating activity were studied after a single i.v. bolus injection of thio-TEPA in six ovarian cancer patients. TEPA was present in serum as of 5 min after drug administration, and its concentration rapidly reached a plateau in the range of 50-100 ng/ml. After about 3 h the serum concentration of TEPA exceeded that of thio-TEPA, and in five of the six patients the metabolite persisted longer than the parent drug in serum. AUCs of thio-TEPA and TEPA were 822 +/- 83 and 1,084 +/- 234 ng h/ml, respectively. The great interindividual variation encountered in the serum pharmacokinetics of TEPA may be of clinical importance and represents a further indication that pharmacokinetically guided dosing of thio-TEPA could be valuable. Urinary recoveries of both thio-TEPA and TEPA were low, together constituting less than 2% of the delivered dose. A substantial gap existed between this and the total urinary alkylating activity, which averaged 13% of the dose in terms of thio-TEPA equivalents. This gap strongly indicates the presence of other unknown metabolites.
Department of Pharmacology and Toxicology, University of Trondheim, Norway.
B
B
Hagen
G
G
Neverdal
R A
RA
Walstad
O G
OG
Nilsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000478:Alkylation; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013852:Thiotepa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013721:Triethylenephosphoramide / Q000493:pharmacokinetics; D014556:Urine / Q000032:analysis
D013852:Thiotepa; D013721:Triethylenephosphoramide