Abstract
PurposeSorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug–drug interactions (DDIs) between sorafenib and paracetamol.MethodsRats were divided into three groups, each consisting of eight animals. The first group received sorafenib (IIS), the second group received sorafenib + paracetamol (IS+PA), whereas the third group received only paracetamol (IIIPA). A single dose of sorafenib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. The plasma concentrations of sorafenib and its metabolite–N-oxide as well as paracetamol and its glucuronide and sulphate metabolites were measured using validated high-performance liquid chromatography (HPLC) method with ultraviolet detection.ResultsThe co-administration of sorafenib and paracetamol increased the maximum concentration (Cmax) of paracetamol by 33% (p = 0.0372). In the IS+ PA group the Cmax of paracetamol glucuronide was reduced by 48% (p = < 0.0001), whereas the Cmax of paracetamol sulphate was higher by 153% (p = 0.0012) than in the IIIPA group. Paracetamol increased sorafenib and sorafenib N-oxide Cmax by 60% (p = 0.0068) and 83% (p = 0.0023), respectively.ConclusionsA greater knowledge of DDI between sorafenib and paracetamol may help adjust dose properly and avoid toxicity effects in individual patients.
Highlights
According to epidemiological data, morbidity and mortality rates due to malignant tumors are continuously increasing
The calibration curve for paracetamol was linear within the range of 1.0–60.0 μg/mL (r = 0.999), for paracetamol glucuronide within the range of 0.2–50.0 μg/mL (r = 0.999), and for paracetamol sulphate within the range of 0.2–60.0 μg/ mL (r = 0.998)
The calibration curve for sorafenib was linear within the range of 0.025–5.0 μg/mL (r = 0.998) and for sorafenib N-oxide within the range of 0.02–0.40 μg/mL (r = 0.999)
Summary
Morbidity and mortality rates due to malignant tumors are continuously increasing. Chemotherapy may be an effective systemic treatment of cancer, but this method has many limitations resulting especially from tumour heterogeneity and acquired cancer cells resistance [1]. Due to insufficient selectivity of drugs and their multidirectional mechanism of action, there is still a problem of serious and life-threatening adverse drug reactions [2]. They contribute to reduction of the quality of patients’ life and may lead to the failure of the therapy. Today’s chemotherapy is frequently based on concomitant administration of classic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
