薬理と治療

Abstract

Objectives The burning pain on injection occurs in approximately 50％-80％ of patients injected with Eslax®（commercial product name of Rocuronium formulation in Japan）and is often associated with the withdrawal movement of the injected hand or arm. In addition, the active ingredient of Eslax(R), Rocuronium bromide, is unstable in solution and it needs to be stored at 2 to 8℃. The purpose of this study was to determine the cause of pain that accompanies the injection of Eslax(R) and to identify the ideal pH to improve the stability of Rocuronium bromide in solution. We developed a Generic Rocuronium, which produced significantly less pain on injection in animal models and the stability at room temperature is also much better compared to Eslax(R). Methods The rat injection pain model was used to determine the cause of pain on injection with Eslax(R). The stability of the active ingredient, Rocuronium bromide, in a variety of pH conditions was demonstrated by HPLC. Sciatic nerve-gastrocnemius muscle preparation was used to evaluate the muscle relaxant effect of the Generic Rocuronium, and a perivascular irritation study in rabbits was performed to evaluate local irritation of the Generic Rocuronium. Results It was clarified that the concentration of the buffer in Eslax(R) is attributable to pain on injection. The most stable pH of Rocuronium bromide was approximately 3. Based on these results, we attempted to develop a Generic Rocuronium, with which pain on injection is relieved and can be stored at room temperature. The muscle relaxant effect of the Generic Rocuronium was the same as that of Eslax(R). A perivascular irritation of the Generic Rocuronium was less than that of Eslax(R). Conclusions Our study indicates that this Generic Rocuronium is useful as an added-value product in terms of less pain on injection and stored at room temperature.