title: Absolute bioavailability and pharmacokinetics of oral teniposide.
abstract: The absolute bioavailability and pharmacokinetics of orally administered teniposide were investigated in 25 patients. All patients received 50 to 60 mg/m2 teniposide intravenously on day 1, before oral administration. Six patients received 60 mg/m2 as a single oral dose on day 8; 5 patients received 60 mg/m2 and 120 mg/m2 as a single oral dose on days 8 and 15, respectively; 5 patients received 120 mg/m2 and 240 mg/m2 as a single oral dose on days 8 and 15, respectively; 6 patients received 60 mg/m2 as a single oral dose on 5 consecutive days from days 8 to 12; and 3 patients received 50 mg/m2 three times a day at 6-hour intervals on day 8. The mean absolute bioavailability was 41.6% +/- 14.2% with a large interindividual variability (range, 19.7% to 71.4%) and a low intraindividual variability (range, 2.8% to 13.9%). At a dose of 240 mg/m2, the bioavailability was decreased, whereas administration of multiple doses on 1 day or 5 consecutive days increased the overall bioavailability. In conclusion, teniposide can be administered orally with a bioavailability comparable with that of etoposide. The schedule dependency of both drugs warrants investigations of oral administration for 21 or more days. A formulation of teniposide capsules of 50 mg or less would be most helpful to facilitate oral administration.
authors.affiliation: Department of Medical Oncology, University Hosptial Dijkzigt, Rotterdam, The Netherlands.
authors.forename: T A
authors.initials: TA
authors.lastname: Splinter
authors.forename: J J
authors.initials: JJ
authors.lastname: Holthuis
authors.forename: T C
authors.initials: TC
authors.lastname: Kok
authors.forename: M H
authors.initials: MH
authors.lastname: Post
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D017321:Clinical Trials, Phase I as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D013713:Teniposide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors
chemical_list: D013713:Teniposide