EFFECT OF VEHICLE AND ROUTE ON CLONAZEPAM LEVELS IN RATS

Clonazepam (CLZ) is a useful anticonvulsant; however, studies using different vehicles and routes have found conflicting results. CLZ levels measured in rats after single dose injections of either intraperitoneal (IP) or subcutaneous (SC) CLZ (1.0 mg/kg) dissolved in either propylene glycol (PG), propylene glycol + 18% ethanol (PGEtOH) or polyethylene glycol (PEG 400) were used to calculate the terminal elimination rate constants (beta), area under the time-concentration curve (AUC) and total clearance (CIT). A two way analysis of variance between route of administration and vehicle showed an effect of route on CIT (P<0.001) which depended on which vehicle was administered. When CLZ was dissolved in PG or PEG 400 the beta and CIT was significantly (P<.05) lower, and the AUC was significantly (P<.05) higher after SC than IP injections. The differences in beta, CIT or AUC between SC and IP injections were not significant when CLZ was dissolved in PGEtOH. SC injections produced more stable and reproducible CLZ levels than IP injections regardless the vehicle used. CLZ injections produce different plasma levels depending on the route and the vehicle used. In order to compare studies of CLZ effects, all of these variables must be considered.