G. Würthwein(1), S. Krümpelmann(2), J. Boos(1)
1)Department of Pediatric Hematology and Oncology, University of Münster, FRG- D-48129 Münster; 2) Darmstädter Kinderkliniken, Dieburgerstr.31, FRG- D-64287 Darmstadt
Introduction: Etoposide acts by inhibition of topoisomerase II, and marked schedule-dependency has been demonstrated. Antitumour effect may be related to duration of exposure to a relatively low serum level while myelosuppression may be dependent on peak etoposide serum levels. With regard to such therapeutic ranges, pharmacokinetic profiles after oral and short time i.v. (1 h infusion) administration of an uniform etoposide dose of 100 mg/m2 were compared.
Methods: Patients were treated within different treatment schedules with i.v. (16 pts, 1 h infusion)1 or oral (18 pts)2 etoposide. Plasma etoposide concentrations were determined by HPLC, and population pharmacokinetic parameters were calculated (P-Pharm 1.4). Duration of exposure and AUC (expressed as percent of total AUC, pAUC) to predefined plasma etoposide concentration ranges were used to compare pharmacokinetic profiles.
Results: Despite an “apparent bioavailability” of 59 %, comparison between oral and i.v. administration of an uniform etoposide dose showed:
-predefined “therapeutic range” of 0.5-3 µg/ml:
same time of exposure and even significantly higher p-AUC after oral compared to i.v.
-probably more myelotoxic concentration range >3 µg/ml:
significant lower time of exposure and highly significant lower p-AUC after oral compared to i.v.
Conclusions: Oral etoposide therapy is at least equivalent compared to short time i.v. therapy in terms of achieving specific target concentration ranges and avoiding peak concentrations.
1. Boos, J., Real, E., Schulze-Westhoff, P., Pröbstin, B. & Jürgens, H. Klin Pädiatr 205, 288-294 (1993).
2. Tillmann, B., Krümpelmann, S., Würthwein, G., et al. Klin.Pädiatr. 210, 159-164 (1998).
Reference: PAGE 8 (1999) Abstr 168 [www.page-meeting.org/?abstract=168]
Poster: poster