Pharmacokinetics of imipramine after single and multiple intravenous administration in rats

Plasma and brain levels of imipramine (IMI) and desmethylimipramine (DMI) in rats after single and multiple iv administration were estimated. IMI accumulated only in plasma, while DMI accumulated in plasma and brain of rats. The brain level of IMI and DMI was higher than plasma level. After multiple administration plasma DMI concentration was significantly greater than IMI concentration. It seems that IMI was obtained steady-state plasma concentration already at fifth day of multiple administration. High dose of IMI (10 mg/kg) caused that the relationship between steady-state concentration and dose of IMI cannot be expressed as a linear function.