Plasma and brain pharmacokinetics of mianserin after single and multiple dosing in mice.

Pharmacokinetics parameters describing the time course of concentrations of mianserin (MIA) in plasma and brain and the relationship between plasma and brain concentrations were studied after acute and chronic administration of increasing doses of MIA in adult mice. There was a linear relationship between the area under the curve (AUC), the maximum concentration (Cmax) and doses, in plasma and brain, both during acute and chronic experiments (p less than 0.05). A five-fold variation in plasma and brain terminal half-life (t 1/2) after chronic administration of the drug was observed, possibly due to a reduction in plasma drug clearance (CL). The values of Cmax and AUC in plasma and brain showed an increase of respectively about three and twelve times after chronic treatment. A very good correlation was observed between plasma and brain Cmax in both acute and chronic experiments; brain Cmax was 10.2 (+/- 0.16) times higher than plasma Cmax after acute administration and 12.08 (+/- 1.33) times higher after chronic administration.