The absolute bioavailability of oral vinorelbine in patients with solid tumors.
Due to advances in the methods used to quantitate vinorelbine, this study was conducted to characterize fully the bioavailability of an oral dosage form of vinorelbine. Twenty-seven eligible patients with solid tumors were enrolled onto this study and were treated in a randomized crossover design to receive either 70 mg/m2 orally or 30 mg/m2 intravenously followed by the alternative treatment one week later. Vinorelbine was administered orally as a soft-gelatin capsule. Pharmacokinetic sampling was carried out for 7 days following each dose. Whole blood vinorelbine concentrations were measured using a sensitive LC/MS/MS method. The data from patients were excluded if they vomited within 3 h after the oral dose.


RESULTS
Three subjects were removed from study following the first dose due to safety reasons. Of the remaining 24 subjects, five experienced vomiting within 3 h of oral dosing. Total body clearance calculated from the intravenous dose was 43.65 L/h (+/-10.9) and the terminal half-life was estimated to be 49 h. Using complete data from the remaining 19 subjects, the mean absolute bioavailability of the oral dosage formulation of vinorelbine was calculated to be 33% (+/-18%). In conclusion we have characterized the pharmacokinetics of both orally administered and intravenous vinorelbine over 7 days after administration and have determined the mean oral bioavailability of this oral formulation to be 33%.
Lush
Richard M
RM
Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, and the Department of Interdisciplinary Oncology, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA. lushrm@moffitt.usf.edu
McCune
Jeannine S
JS
Tetteh
Leticia
L
Thompson
John A
JA
Mahany
J J
JJ
Garland
Linda
L
Suttle
A Benjamin
AB
Sullivan
Daniel M
DM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine; D014839:Vomiting / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine