Effect of smoking on imatinib pharmacokinetics

• Published in: Journal of clinical oncology Vol. 25; no. 18_suppl; p. 2573
• Main Authors: van Erp, N. P., Gelderblom, H., van Glabbeke, M., van Oosterom, A., Verweij, J., Guchelaar, H., Peng, B., Judson, I.
• Format: Journal Article
• Language: English
• Published: 20.06.2007
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2007.25.18_suppl.2573

Abstract only 2573 Background: Smoking is a potent inducer of the cytochrome P450 1A2 isoenzyme (CYP1A2) and may therefore effect the pharmacokinetics (PK) of drugs metabolized by CYP1A2. Indeed, clinical studies with erlotinib (metabolized by CYP3A4 and also partly by CYP1A2) have shown a major increase in erlotinib clearance in smokers versus non-smokers. The effect of smoking on the PK of imatinib, which is also metabolized by CYP3A4 and partly by CYP1A2, is unknown. We aimed to study the effect of smoking on imatinib PK in order to explain a part of the interpatient variation. Methods: The effect of smoking on the PK parameters was analyzed in 34 patients with gastro-intestinal stromal tumors or soft tissue sarcoma included in the EORTC-STBSG phase I and phase II trials. This cohort included 9 smokers and 25 non-smokers. The daily smoking habits of the study patients were retrieved retrospectively from the patient’s record. PK parameters assessed with NONMEM, version V were clearance (Cl), distribution volume (V), elimination half life (T1/2) and the dose standardized area under the concentration curve (AUC). We considered a 40% reduction in imatinib exposure clinically relevant and this study is adequately powered to detect this difference. Results: The mean PK parameters in the smokers versus the non-smokers group ± SD were: Cl; 9.6 ± 5.5 L/h vs 9.2 ± 4.6 L/h, V; 216.5 ± 114.3 L vs 207.0 ± 116.9 L, T1/2; 16.1 ± 6.0 h vs 16.5 ± 6.0 h, AUC; 133.6 ± 71.0 ng.h/ml.mg vs 142.3 ± 84.0 ng.h/ml.mg. There was no significant difference in PK parameters observed between the smokers and the non- smokers. Conclusion: This retrospective study suggest that the PK of imatinib was not affected by smoking and therefore does not explain the large variation in imatinib PK. No significant financial relationships to disclose.