Abstract
Background
Gefitinib (IRESSA) is normally administered as a once-daily oral tablet. However, many patients with head and neck cancer have difficulty swallowing medication in a tablet form. A granular formulation has recently been developed to facilitate the administration of gefitinib to patients who are unable to swallow tablets.
Objectives
The aims of this study were to determine the relative bioavailability of a single dose of gefitinib when administered as 250 mg of a new granular formulation compared with the standard 250 mg tablet, and to assess the intra-subject variability of the granular formulation, in healthy subjects.
Methods
This was a randomized, open-label, three-period crossover study. Healthy male subjects (n = 18) received either a single gefitinib 250 mg tablet (once), or a 250 mg granular formulation of gefitinib (on two separate occasions) over the three dosing periods, in randomized order. Plasma concentrations of gefitinib were measured up to 240 h post-dose.
Results
The treatment ratio estimates for area under the plasma concentration versus time curve (AUC) and peak plasma concentration (C max) for the granular formulation when compared with the tablet were 1.05 (90% confidence intervals [CI] for the ratio 0.97–1.13) and 1.14 (90% CI for the ratio 1.01–1.28), respectively. The estimate for the intra-subject standard deviation for the granular formulation when given on 2 separate occasions was 0.143 for AUC and 0.165 for C max, equivalent to a 1.4- and 1.7-fold intra-subject variability in AUC and C max, compared with that observed for the tablet of two and threefold, respectively.
Conclusions
There was little difference in exposure to gefitinib administered as the 250 mg granular formulation compared with the 250 mg standard tablet. The granular formulation of gefitinib could provide an alternative treatment regimen for patients unable or unwilling to swallow the standard tablet formulation, without compromizing exposure to gefitinib.
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Acknowledgments
The authors thank Analytico Medinet BV (The Netherlands) for performing the gefitinib assays and Anna Marshall for providing the statistical analysis of the study data. We thank Dr Annette Smith, from Complete Medical Communications, who provided editing assistance funded by AstraZeneca. IRESSA is a trademark of the AstraZeneca group of companies. We thank the Alderley Park study team for the development of the protocol and delivery of the study report and the staff of the Alderley Park Clinical Pharmacology Unit for performing the resident phase of the study, and biological sample preparation. The study described here complies with the current laws of the UK, inclusive of ethics approval.
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Cantarini, M.V., Bailey, C.J., Collins, B. et al. The relative bioavailability of gefitinib administered by granular formulation. Cancer Chemother Pharmacol 62, 203–208 (2008). https://doi.org/10.1007/s00280-007-0589-2
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DOI: https://doi.org/10.1007/s00280-007-0589-2