Investigation of bioavailability and pharmacokinetics of treosulfan capsules in patients with relapsed ovarian cancer |
| |
Authors: | Ralf Axel Hilger Gabriele Jacek Carsten Oberhoff Susanne Kredtke Joachim Baumgart Siegfried Seeber Max Ernst Scheulen |
| |
Institution: | Innere Klinik und Poliklinik (Tumorforschung), Universit?tsklinikum Essen, Westdeutsches Tumorzentrum, Hufelandstrasse 55, 45122 Essen, Germany e-mail: ralf.hilger@uni-essen.de Tel.: +49-201-7233157; Fax: +49-201-7233790, DE Zentrum für Frauenheilkunde, Abteilung für Gyn?kologie, Universit?tsklinikum Essen, Westdeutsches Tumorzentrum, Essen, Germany, DE Medac GmbH, D-20354 Hamburg, Germany, DE
|
| |
Abstract: | Purpose: Treosulfan (l-threitol-1,4-bis-methanesulfonate, Ovastat) is a prodrug of a bifunctional alkylating agent with activity in ovarian carcinoma
and other solid tumors. In a pharmacologic study of the bioavailability of treosulfan in a capsule formulation, patients with
relapsed ovarian carcinoma were treated with alternating doses of oral and intravenous (i.v.) treosulfan of 1.5 or 2.0 g daily
for 5 to 8 days. Methods: A sensitive method for the determination of treosulfan in plasma and urine by reversed-phase high-performance liquid chromatography
had previously been developed. Pharmacokinetic analyses of treosulfan were carried on plasma and urine samples from 20 i.v.
courses and 20 courses of oral administration. Results: The bioavailability ratio (f) of oral to i.v. administration was calculated as 0.97 ± 0.18 (mean ± SD) using the values AUCoral=82.1 ± 39.4 μg/ml h and AUCi.v.=85.4 ± 30.3 μg/ml h. The peak plasma concentration cmax (29 ± 14 μg/ml vs 65 ± 23 μg/ml) was significantly (P < 0.01) higher after i.v. administration and the tmax after oral administration was 1.5 ± 0.34 h. The terminal half-life of treosulfan was about 1.8 h. The mean urinary excretion
of the parent compound was about 15% of the administered total dose over 24 h (range 6–26%). Conclusions: The high and relatively constant bioavailability of treosulfan indicates that capsules provide a satisfactory noninvasive
treatment alternative. A feasible and reliable oral treosulfan formulation could provide the basis for the development of
long-term low-dose outpatient treatment of patients with malignant diseases.
Received: 28 July 1999 / Accepted: 16 December 1999 |
| |
Keywords: | Treosulfan Bioavailability Dihydroxybusulfan Pharmacokinetics Ovarian carcinoma |
本文献已被 PubMed SpringerLink 等数据库收录! |
|