3 minute read
Assessment of the effect of
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
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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.
MATERIAL AND METHODS: The animals 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.
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 – 107.1).
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).
Questions & answers
Please, tell us a little bit more about yourself. My name is Karina Kordalewska and I’m a final year student at Faculty of Pharmacy in Poznan, Poland. Currently I am an obligatory intern at a community pharmacy. During my studies I started to become interested in clinical pharmacy, especially in oncology. Unfortunately a clinical pharmacist position in Poland is not common, but after graduation I aspired to be a part of the GP team and participate in patient care with other health workers. I also love to travel, especially by hitchhiking or with a van. In my free time I like to do yoga and play on the ukulele.
Tell us a bit more about your research and its significance. My research was about the effect of morphine on the sorafenib pharmacokinetic profile. Sorafenib is a tyrosine kinase inhibitor which is indicated in the treatment of hepatocellular carcinoma, advanced renal cell carcinoma and thyroid cancer resistant to radioactive iodine. Patients diagnosed with cancer often suffer from chronic pain, where opioid analgesics are considered to be on the first place in the treatment of moderate to severe pain. The aim of the study was to investigate the possible pharmacokinetic interaction between these two drugs. to investigate in humans. At first we had to submit the application for ethical approval of an animal experiment to the local ethical committee. After we got the approval it was necessary to prepare animals for the research - ensure the appropriate conditions for them (systematic feeding and cleaning, checking the temperature, humidity, lighting) and familiarize them with persons performing the experiment.
In your opinion, what is the benefit of joining ESSP and what advice do you have for students undertaking research in the future? Joining ESSP gives a chance to publish your research and share your work with other students from other countries. It can be one of your first steps in science. To all students that are considering doing research projects I would say give yourself time and be patient. Don’t expect huge accomplishments in a short period. Reward yourself with every little step during the whole process. Then you won’t lose your motivation and the satisfaction of every goal that you reach will be indescribable.
What was the biggest challenge while carrying out the research and how did you overcome that? This study had to be conducted on laboratory rats as we wanted to estimate the influence of morphine on sorafenib’s pharmacokinetic parameters, which was very challenging
