Pharmacokinetics and tolerability of the orally active selective epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in healthy volunteers

To investigate the pharmacokinetics and tolerability of ZD1839 (Iressa), an orally active selective epidermal growth factor receptor-tyrosine kinase inhibitor, in healthy volunteers. Two randomised, double-blind, placebo-controlled, parallel-group studies of pharmacokinetics and tolerability, follow...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2001, Vol.40 (4), p.297-306
Main Authors: SWAISLAND, Helen, LAIGHT, Alison, STAFFORD, Lesley, JONES, Helen, MORRIS, Charles, DANES, Aaron, YATES, Roger
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antineoplastic agents
Area Under Curve
Biological and medical sciences
Double-Blind Method
Electrocardiography - drug effects
Enzyme Inhibitors - adverse effects
Enzyme Inhibitors - pharmacokinetics
General aspects
Half-Life
Humans
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Quinazolines - adverse effects
Quinazolines - pharmacokinetics
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Treatment Outcome
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Summary:To investigate the pharmacokinetics and tolerability of ZD1839 (Iressa), an orally active selective epidermal growth factor receptor-tyrosine kinase inhibitor, in healthy volunteers. Two randomised, double-blind, placebo-controlled, parallel-group studies of pharmacokinetics and tolerability, followed by a nonblind, randomised, 2-period crossover study to assess the effect of food on bioavailability. Two centres in the UK. Healthy male volunteers aged between 18 and 62 years. The first study investigated the pharmacokinetics and tolerability of ascending single oral doses of ZD1839 (1 to 75mg). The second study investigated the pharmacokinetics and tolerability of multiple doses of ZD1839 (100mg once daily for 3 days). The third study investigated the effect of food on the bioavailability of a single 50mg dose of ZD1839. Peak plasma drug concentrations (Cmax) of ZD 1839 occurred between 3 and 7 hours after administration. Cmax and area under the concentration-time curve (AUC) were dose-proportional from 10 to 100mg. The terminal elimination half-life (t1/2beta) was 28 hours (range 12 to 51 hours). Cmax was reduced by 34% and AUC by 14% by ingestion of food; t1/2beta was not affected. Urinary recovery of ZD1839 was
ISSN:0312-5963
1179-1926
DOI:10.2165/00003088-200140040-00005