精密持続点滴中のタクロリムス注射液の含量低下とフタル酸ジ-2-エチルヘキシルの溶出

Abstract

A tacrolimus injection is an immunosuppressant which is administered by an intravenous injection of drip infusion over a period from 4-24 hours. We herein investigated the factors effecting the loss of tacrolimus from the intravenous solution, and leaching di-2-ethylhexyl phtalate (DEHP, specified environmental estrogen) from the administration tube into the intravenous solution. The concentrations of tacrolimus and DEHP were measured by high-performance liquid chromatography (HPLC). The factors effecting the loss of tacrolimus from intravenous solutions were thus found to be the length and the inside diameter of the administration apparatus, the concentration of the tacrolimus solution and the drip rate of the solution. When the tacrolimus solution passed through an administration tube consisting of polyvinyl chloride (PVC) measuring 100 cm in length at a flow rate of 5.0 mL/h and an initial concentration 50μg/mL, the concentration of tacrolimus decreased to about 76% and 12μg/mL of DEHP leaked into the solution per hour. On the other hand, when using polyethylene or polyolefin tubes, the amount of tacrolimus did not decrease and no DEHP leaked into the solution. Therefore, when tacrolimus is administered in travenously in a solution from, PVC administation tubes should not be used.