A new method of consistency evaluation of brain drugs: a case study of edaravone.

Bioequivalence test is typically conducted by determining the drug concentration in plasma. However, this is not suitable for brain drugs (like Edaravone) that have targets in CNS. The amount of a drug in target site in the CNS is responsible for its activity in the brain, while the concentration of a drug in the blood has a weak impact on the CNS. In this paper, a new consistency evaluation method for brain drugs was established. 16 rats were divided into two groups. One group was administered the test preparation, and the other group was administered the control preparation. Then, cerebrospinal fluid (CSF) samples were collected. All of the CSF samples were examined by LC-MS. The 90 % confidence interval of the geometric mean ratio of AUC0-t was 90.30-150.59 %, and 91.79-211.06 % for Cmax. In addition, the result indicated that the two preparations were not bioequivalent in the CNS, although the concentration-time profile and pharmacokinetic parameters were quite similar. The results revealed the particularity and complexity of the bioequivalence test for brain drugs that have targets in the CNS. The feasibility of the test was confirmed, and our results provide useful information for the consistency evaluation of brain drugs.