Pharmacokinetics of clonazepam in developing rats

Time-concentration studies of clonazepam (CZP) were performed in 7-, 14-, and 28-day-old Sprague-Dawley rats. Blood samples and brains were collected at specific intervals following a single subcutaneous (SC) injection of 2.5 mg/kg of CZP. CZP concentrations were measured both in plasma and brain samples by high performance liquid chromatography. Pharmacokinetic parameters were calculated using R-Strip for each age group. The results were compared between the age groups and with those of a similar study in our laboratory using lower dose CZP (1 mg/kg) SC injections in adult Sprague-Dawley rats. Younger rats had slower, delayed and higher peak concentrations, larger areas under the curve (AUC), longer elimination half lives (T1/2), smaller volumes of distribution (Vd) and slower clearances (C1). 28-day-old rats showed the fastest C1, smallest AUC and largest Vd. These data suggest that the pharmacokinetic behavior of CZP is age-dependent. If this is true in human, it is implicated in dosing of neonatal or pediatric patients.