Single and repeated dose pharmacokinetics of thio-TEPA in patients treated for ovarian carcinoma

Summary

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 elemination half-life (3.86±0.97 h), which could be of clinical relevance.

A first-order elimination process with a short elimination half-life (∼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.