Hilger RA, Richly H, Grubert M, Kredtke S, Thyssen D, Eberhardt W, et al,. Pharmacokinetics of Sorafenib in Patients with Renal Impairment Undergoing Hemodialysis. Int J Clin Pharmacol Ther.; 2009: 47(1); 61-64.
This study was focusing on the use of Sorafenib for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. It is a molecular inhibitor of a variety of tyrosine protein kinases and Raf kinases. Sorafenib is an oral inhibitor that inhibits the activity of threonine kinases. It has been approved in many countries including United States for the treatment of advanced renal cancer and primary liver cancer. Sorafenib has a mean half life of approximately 25-48 hours. After oral administration, 19% of the drug is excreted in urine and 77% in feces.17% of Sorafenib circulated in plasma in the form of Sorafenib N-oxide. This study conducted two mechanisms; glucuronidation and excretion of metabolites from the gall balder and reabsorption of Sorafenib and oxidation and excretion of metabolites.
The main objective of this study was to analyze the feasibility of the application of Sorafenib to patients who have renal impairment and are undergoing Hemodialysis. Thus, the study was to analyze the pharmacokinetics of Sorafenib suffering from renal impairment to determine the influence of Hemodialysis. In simple terms, the study was to analyze the absorption of Sorafenib in patients suffering from renal dysfunction when undergoing Hemodialysis.
The study uses a qualitative research method. Two patients who were undergoing Hemodialysis were treated with the drug. The first patient received 200mg of Sorafenib two times a day. Prior to the process of Hemodialysis, the patient did not receive the dose of Sorafenib in the morning, which was compensated by 400 mg of Sorafenib after Hemodialysis. For pharmacokinetics analysis, blood samples were taken every 20 minutes for 2 hours after administration of the morning dose. This was followed by hourly blood withdrawal for six hours. Samples were obtained to get information about Sorafenib blood levels before and after Hemodialysis. The second patient received 200mg of the drug every morning. Blood samples were taken prior to application of the drug which was followed by repeated drawing every 30 minutes for ten hours.
Result for the first patient who was suffering from hepatocellular carcinoma shows that renal excretion at 19% within two weeks after a single application. There was no detection of Sorafenib or its corresponding metabolites in urine of the patient. This suggested low renal excretion of Sorafenib.
Pharmacokinetic analysis of the second patient showed no accumulation from the first dose of Sorafenib. The results were best calculated using a four segment absorption model with elimination. The tests uncovered an effect of Sorafenib from blood samples taken during Hemodialysis.
This journal article is not conclusive. The methodology is not discussed in details making it hard for the reader to understand. The study also did not have a clear discussion of the data collected. The presentation of data is also scanty as the four graphs cannot be understood easily. Thus, someone has to rely on the results part to understand it. This shows that the graphs are not useful at all to the study.
Reference
Hilger RA, Richly H, Grubert M, Kredtke S, Thyssen D, Eberhardt W, et al,. Pharmacokinetics of Sorafenib in Patients with Renal Impairment Undergoing Hemodialysis. Int J Clin Pharmacol Ther.; 2009: 47(1); 61-64.
