July 25, 2016
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Thiotepa (thiotepa (thiotepa injection) injection) is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to nitrogen mustard. The radiomimetic action of thiotepa (thiotepa (thiotepa injection) injection) is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.

The pharmacokinetics of thiotepa (thiotepa (thiotepa injection) injection) and TEPA in thirteen female patients (45 to 84 years) with advanced stage ovarian cancer receiving 60 mg and 80 mg thiotepa (thiotepa (thiotepa injection) injection) by intravenous infusion on subsequent courses given at 4-week intervals are presented in the following table:

Pharmacokinetic Parameters (units) Mean± SEM
Thiotepa TEPA
60 mg 80 mg 60 mg 80 mg
Peak Serum concentration (ng/mL) 1331 ± 119 1828 ± 135 273 ± 46 353 ± 46
Elimination half-life (h) 2.4 ± 0.3 2.3 ± 0.3 17.6 ± 3.6 15.7 ± 2.7
Area under the curve (ng/h/mL) 2832 ± 412 4127 ± 668 4789 ± 1022 7452 ± 1667
Total body clearance (mL/min) 446 ± 63 419 ± 56    

TEPA, which possesses cytotoxic activity, appears to be the major metabolite of thiotepa (thiotepa (thiotepa injection) injection) found in human serum and urine. Urinary excretion of 14C-labeled thiotepa (thiotepa (thiotepa injection) injection) and metabolites in a 34-year old patient with metastatic carcinoma of the cecum who received a dose of 0.3 mg/kg intravenously was 63%. Thiotepa (thiotepa (thiotepa injection) injection) and TEPA in urine each accounts for less than 2% of the administered dose.

The pharmacokinetics of thiotepa (thiotepa (thiotepa injection) injection) in renal and hepatic dysfunction patients have not been evaluated. Possible pharmacokinetic interactions of thiotepa (thiotepa (thiotepa injection) injection) with any concomitantly administered medications have not been formally investigated.

Last reviewed on RxList: 11/20/2008
This monograph has been modified to include the generic and brand name in many instances.

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