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...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2005-12, Vol.56 (6), p.578-584
Main Authors: LUSH, Richard M, MCCUNE, Jeannine S, TETTEH, Leticia, THOMPSON, John A, MAHANY, J. J, GARLAND, Linda, SUTTLE, A. Benjamin, SULLIVAN, Daniel M
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Aged
Antineoplastic agents
Antineoplastic Agents, Phytogenic - adverse effects
Antineoplastic Agents, Phytogenic - pharmacokinetics
Area Under Curve
Biological and medical sciences
Biological Availability
Dose-Response Relationship, Drug
Drug Administration Routes
Female
Humans
Injections, Intravenous
Intestinal Absorption
Male
Medical sciences
Middle Aged
Neoplasms - drug therapy
Neoplasms - metabolism
Pharmacology. Drug treatments
Vinblastine - adverse effects
Vinblastine - analogs & derivatives
Vinblastine - pharmacokinetics
Vomiting - chemically induced
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Summary: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. 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%.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-005-1025-0