Single and repeated dose pharmacokinetics of thio-TEPA in patients treated for ovarian carcinoma.
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| Abstract |
Triethylenethiophosphoramide (thio-TEPA) pharmacokinetics were studied in 15 patients being treated for epithelial ovarian carcinoma. Unchanged thio-TEPA was assayed in serum and urine by means of a gas chromatographic procedure. No accumulation or alteration of the pharmacokinetics occurred during therapy, which was continued for up to 7 months with biweekly administrations of 20 mg, after two initial loading courses with 20 mg daily for 3 consecutive days 2 weeks apart. No significant difference in the pharmacokinetics between i.m. and i.v. administration was demonstrated. However, three patients showed a reduced absorption ability from the i.m. injection site to the systemic circulation and an apparent increase in the elimination half-life (3.86 +/- 0.97 h), which could be of clinical relevance. A first-order elimination process with a short elimination half-life (approximately 1.5 h) was demonstrated for thio-TEPA in all patients after i.v. administration. The apparent volume of distribution averaged 50 1. The renal clearance was below 1% of the total-body clearance, which averaged 412 ml/min. The urinary excretion of unchanged thio-TEPA was complete within 8 h after administration, with an average urinary recovery of 0.14% of the dose. Calculation of the area under the serum concentration vs time curve revealed wide variation between patients (range 517-1480 ng/h ml-1), indicating the need for drug monitoring during therapy.
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| Authors | B Hagen, F Walseth, R A Walstad, T Iversen, O G Nilsen |
| Journal | Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 19 Issue 2 Pg. 143-8 ( 1987) ISSN: 0344-5704 [Print] Germany |
| PMID | 3105905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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