LONG-TERM PHARMACOKINETICS OF THIO-TEPA, TEPA AND TOTAL ALKYLATING ACTIVITY FOLLOWING IV 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 consituting <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. © 1990 Springer-Verlag.