Toxic interactions of Romiplostim and Rituximab in normal and thrombocytopenic Rats

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immunologic destruction of normal platelets and insufficient production of platelets mediated by autoantibodies. And there are different treatment options for management of thrombocytopenia according to each case. Because of the progression of the disease and its multiple pathophysiological pathways a combination of treatments used for management of ITP would be a point of interest. Co-administration of therapies may be useful in patients who are refractory to monotherapies and may result in a booster response because they target multiple mechanisms. Romiplostim is a potent drug used for the management of acute ITP and can be administered with other treatment options for ITP. The combination of Rituximab and Romiplostim may inhibit platelet destruction and at the same time increase platelet production. This combination can lead to a strong and a massive increase in platelet counts. In preclinical studies of Romiplostim safety margins could not be reliably estimated. Although some post marketing surveillance studies provided some information about the safety profile of this drug. More information is needed to evaluate drug interactions between Romiplostim and Rituximab.The goal of this study is to investigate the safety of co-treatment of Romiplostim with Rituximab as compared to each of these drugs in normal rats and thrombocytopenic rats. The measured safety parameters were evaluated for liver and kidney functions in normal and diseased groups of rats.The safety of this regimen should be taken in consideration, so that a balance between the harmful effects and beneficial response could be attained. Future studies are necessary to investigate the safety and efficacy balance of Romiplostim and Rituximab alone or in combination with each other for management of thrombocytopenia.

Keywords

• immune thrombocytopenia (itp)
• rats
• romiplostim
• rituximab and thrombopoietin receptor agonists (tpo-ras)