The effect of dose on the bioavailability of oral etoposide: confirmation of a clinically relevant observation.
The effect of dose on the bioavailability of oral etoposide was investigated in ten patients with malignant mesothelioma who received single-agent etoposide as part of a phase II study. Etoposide pharmacokinetics were studied in each patient at oral dose levels of 100, 200, 300, 400 and 600 mg. At doses above 200 mg, the AUC and peak concentrations of etoposide were substantially lower than predictions based on the 100-mg dose. This study confirms previous observations that etoposide absorption is dose-dependent and that a mean bioavailability of approximately 50% cannot be assumed at total oral doses greater than 200 mg.
Slevin
M L
ML
Imperial Cancer Research Fund Department of Medical Oncology, St. Bartholomews Hospital, London, England.
Joel
S P
SP
Whomsley
R
R
Devenport
K
K
Harvey
V J
VJ
Osborne
R J
RJ
Wrigley
P F
PF
D000284:Administration, Oral; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism; D012044:Regression Analysis; D013997:Time Factors
D005047:Etoposide