Impact of imatinib on the pharmacokinetics and in vivo efficacy of etoposide and/or ifosfamide

摘要: Using a human small cell lung cancer (SCLC) xenografted in nude mice, we have previously reported enhanced tumor growth inhibition following chemotherapy combination with imatinib (STI571). We therefore investigated the vivo impact of on pharmacokinetics and efficacy chemotherapy. Two different tumors were used: SCLC6 LY-3 EBV-associated B-cell lymphoma SCID mice. Plasma, urine, fecal concentrations etoposide (VP16) determined by validated high performance liquid chromatography method. Plasma ifosfamidewere gas assay nitrogen-phosphorus detection. Slight was induced administered alone one lymphomatous xenograft. In contrast, an increase chemotherapy-induced antitumor effect observed model but not when mice bearing treated concomitantly This influenced concomitant administration fluconazole. The AUC0-3 h (Area Under concentration-time Curve) increased + due to decreased excretion. did appear influence urinary excretion etoposide, CYP3A4 inhibitor, fluconazole, modify plus alone. Altogether, these results justify further prospective phase I II clinical trials combinations etoposide-based patients certain cancers, such as malignant lymphoma, careful toxicologic monitoring.