Regional distribution and elimination kinetics of imipramine in rat brain after multiple dosages.

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Abstract
The elimination of imipramine (IMP) from brain regions was investigated in rats after multiple intraperitoneal (i.p.) administration for 3 weeks. Brain regions could be divided into two classes as to IMP elimination in analogy with a single i.p. dose. IMP levels in the plasma, class A brain regions (cerebellum, mid-brain and medulla, striatum, posterior cortex and frontal cortex) and the initial phase of the curves for class B brain regions (hypothalamus, thalamus, hippocampus and nucleus accumbens) had identical elimination rate constants. They shifted in parallel depending on the dose as in the case of a single dose. On the other hand, the later phase of the curves in the class B brain regions shifted in parallel to the low concentration side with an elimination rate constant similar to that after a single dose. The high-affinity sites for IMP in class B brain regions seemed to be markedly decreased by multiple doses for 3 weeks.