Resveratrol alters erlotinib pharmacokinetics in rats: application of a rapid HP...

연구 요약

Resveratrol alters erlotinib pharmacokinetics in rats: application of a rapid HPLC-fluorescence method for quantifying erlotinib in plasma.

Naunyn-Schmiedeberg's archives of pharmacology 학술지에 발표된 이 연구는 Zayed AL, Hroot JA, Darweesh RS 외 연구팀이 수행하였습니다.

이 연구는 'Resveratrol alters erlotinib pharmacokinetics in rats: application of a rapid HPLC-fluorescence method for quantifying erlotinib in plasma.'에 대한 과학적 분석을 제공합니다.

핵심 내용

BACKGROUND: Resveratrol is a natural compound and commonly used dietary supplement, especially for its anticancer properties. However, there is a lack of pharmacokinetic (PK) studies investigating its interactions with anticancer drugs, including tyrosine kinase inhibitors (TKIs). This study aimed to investigate the effect of resveratrol on erlotinib pharmacokinetics, a TKI indicated for non-small-cell lung cancer (NSCLC). Another aim was to develop and validate a new high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method as a simple and cost-effective assay to quantify erlotinib levels in rat plasma in vivo. METHODS: HPLC-FLD was used to develop and validate a method for quantifying erlotinib in rat plasma. A PK study was conducted with four groups of male Sprague-Dawley rats: erlotinib (20 mg/kg) alone, erlotinib with either single or multiple doses of resveratrol (100 mg/kg), and a control group. Blood samples were collected and analyzed by HPLC-FLD, and the PK parameters were estimated. RESULTS: A 4-min runtime HPLC-FLD method was developed and validated. Single and multiple doses of resveratrol significantly increased the total area under the curve AUC 0 ∞ , by approximately 2- and 3-fold, respectively, while both decreased the clearance (Cl/F) of erlotinib by approximately 2-fold. CONCLUSION: Resveratrol, even at a single dose, can alter erlotinib pharmacokinetics which may cause clinically relevant drug interactions, particularly considering erlotinib significant interindividual variability and narrow therapeutic index. The new HPLC-FLD method is a reliable, simple, and cost-effective assay that can be used in erlotinib PK studies and therapeutic drug monitoring.

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