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Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i. v. bolus administration of thio-TEPA in ovarian cancer patients

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Summary

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.

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Authors and Affiliations

  1. Department of Pharmacoloy and Toxicology and Department of Gynecology and Obstetrics, University of Trondheim, N-7030, Trondheim, Norway

    Bjørn Hagen, Gunhild Neverdal, Rolf A. Walstad & Odd G. Nilsen

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  1. Bjørn Hagen
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  2. Gunhild Neverdal
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  3. Rolf A. Walstad
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  4. Odd G. Nilsen
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Additional information

The work described in this paper was supported by grants from The Regional Hospital (Trondheim), Trondheim Cancer Society (Trondheim) and The Norwegian Cancer Society (Oslo). During the work Bjørn Hagen was a research fellow for The Norwegian Cancer Society

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Hagen, B., Neverdal, G., Walstad, R.A. et al. Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i. v. bolus administration of thio-TEPA in ovarian cancer patients. Cancer Chemother. Pharmacol. 25, 257–262 (1990). https://doi.org/10.1007/BF00684882

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  • DOI: https://doi.org/10.1007/BF00684882

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