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See Latest ArticlesPopulation pharmacokinetics of erlotinib and its pharmacokinetic/pharmacodynamic relationships in head and neck squamous cell carcinoma
European Journal of Cancer, 06/15/09
Thomas F et al. - Study concludes that erlotinib treatment may present criteria justifying dose individualisation but further studies, including more patients, are necessary to define the modalities of this adaptation.
Methods- Study was undertaken to:
- Analyse the impact of several covariates on the pharmacokinetics of erlotinib and its main metabolite (OSI-420) and
- Determine pharmacokinetic/pharmacodynamic (PK/PD) relationships
- Plasma concns of erlotinib and OSI-420 of 42 pts were analysed to evaluate the impact of pts’ covariates on erlotinib PK
- Presence of SNP in ABCB1 (2677G > T/A and 3435C > T), ABCG2 (421C > A) and CYP3A5 (6986G > A) was investigated
- PK/PD relationships between plasma drug exposure (AUC) and early drug response or toxicity were also studied
- Covariates retained to predict erlotinib clearance were ALAT (alanine amino transferase), age and ABCG2 polymorphism
- A significant link between drug exposure and the grade of skin rash was observed
- However, early response to treatment was not correlated to the erlotinib AUC
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