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European Pharmaceutical Students’ Association
ASSESSMENT OF THE EFFECT OF MORPHINE ON THE OXIDATION PROCESS OF SORAFENIB Authors: Kordalewska Karina, Karbownik Agnieszka, Szałek Edyta, Grabowski Tomasz, Urjasz Hanna, Grześkowiak Edmund Scientific Coordinator: assoc. prof. Szałek Edyta, PhD Institution: Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, Poland
INTRODUCTION: Sorafenib (SR) is a tyrosine kinase inhibitor with high activity towards several families of tyrosine kinases involved in angiogenesis and tumor cell proliferation. The clinical use of sorafenib is indicated in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma and thyroid cancer resistant to radioactive iodine. Opioid analgesics are considered to be on the first place in the treatment of moderate to severe pain for patients diagnosed with cancer, where morphine plays a significant role. Sorafenib is mainly metabolized in the liver with N-oxidation via CYP3A4 to pyridine-N-oxide (N-oxide sorafenib; NO-SR) and glucuronidation via the phase II enzyme UGT1A9. AIM: The aim of this study was to estimate the effect of morphine on the oxidation process of sorafenib to its’ active metabolite: N-oxide sorafenib.
CONCLUSION: The study showed that morphine has no significant influence on the oxidation process of sorafenib. The reason may be high values of coefficients of variation calculated for the control group (%CV = 58.7 MATERIAL AND METHODS: The animals – 107.1). participating in the study were assigned to two groups: study group (n=8) and control group (n=8). Sorafenib was administered orally at the dose of 100 mg/kg, while morphine intraperitoneally at the dose 5 mg/kg concomitantly with sorafenib. The plasma sorafenib and N-oxide sorafenib concentrations were measured using high performance liquid chromatography with UVVIS detection ( =265nm). The PK parameters were determined and calculated using a noncompartmental model. RESULTS: The mean values of PK parameters with standard deviations [SD] for NO-SR/SR ratios in the study group and control group were as follows: Cmax=0.07 [0.02] vs. 0.12 [0.13] ng/ml (p=0.1152), AUC0-t= 0.10 [0.07] vs. 0.08 [0.06] ng*h/ml (p=0.4622), AUC0-∞= 0.12 [0.08] vs. 0.14 [0.08] ng*h/ml (p=0.4622).
