Brain distribution and kinetics of desipramine in the rat

Pharmacokinetics and regional as well as subcellular brain distribution of desipramine (DMI) were investigated in male rats after single and repeated intraperitoneal administration. After a single dose DMI enters brain rapidly, accumulates with increasing the dose, and attains concentrations about 20 times those seen in plasma. After repeated administration peak plasma and brain levels were 2.7 and 3.7 times, respectively, higher than after a single dose. No significant regional differences were found in brain distribution or disappearance half-lives of the drug. After chronic treatment the drug was preferentially retained in the P2 fraction of brain homogenate; this may reflect the critical portion of drug bound to sites responsible for its pharmacological action.