Study on changes of clonazepam¬ðs concentration in rat brain and serum

    YANG Lin1, ZHAO Mei1, XIAO Lin2, HUANG Shaoª²Ping1

    1Department of Pediatric, Second Hospital, Xi¬ðan Jiaotong University, Xi¬ðan 710004, China, 2Xi¬ðan Red Cross Hospital, Xi¬ðan 710054, China

    ¡¾Abstract¡¿ AIM: To determine a reasonable clinical administration protocol by comparing the changes of clonazepam (CZP) concentrations in rat brain and serum following single and repeatedª²dose administration of CZP. METHODS: SD rats were divided into singleª²dose group, repeatedª²dose group, repeatedª²dose at different time points group and repeated dose decreasing group. The animals received CZP intraperitoneally and the concentrations of CZP in the serum and brain were determined by high performance liquid chromatography (HPLC). RESULTS: In single dose group, the concentration of CZP decreased rapidly, especially in the brain. In rats receiving repeated administration of CZP at the time point of 30 min, the CZP concentration in serum and brain increased rapidly. The CZP concentration ratio in both brain and serum of repeatedª²dose group was 1.0 at the time point of 30 min, significantly higher than that of singleª²dose group (0.5). In repeated dose decreasing group, the CZP concentration ratio in both brain and serum declined to 0.7 with the dose decrease, almost the same as that of singleª²dose group. CONCLUSION: Repeated administration of CZP leads to drug accumulation in the body, thus increasing its toxic effects. But repeated administration of dose decreasing CZP will maintain the drug¬ðs potency without substantially increasing its toxicity. ......