Increased bioavailability of clomipramine after sublingual administration in rats

This study examined the absorption and disposition of clomipramine in rats after sublingual (5 and 50 mg/kg), oral (50 mg/kg), and iv (5 mg/kg) admini stration. The mean oral bioavailability of clomipramine was 24.8% and 29.7% , respectively, in conscious rats and in rats anesthetized with ketamine/xy lazine (30/3 mg/kg). When given sublingually in isotonic saline at a dose o f 50 mg/kg, clomipramine was rapidly absorbed, and the mean absolute bioava ilability (36.2%) was increased over oral dosing. The mean AUG values of cl omipramine were 2258 +/- 1762 ng.h/mL and 1891 +/- 867 ng.h/mL after oral a dministration to conscious and anesthetized rats, respectively, and 3303 +/ - 1576 n.gh/mL after sublingual administration to anesthetized rats. Sublin gual administration (5 mg/kg doses) of clomipramine formulated with a perme ation enhancer, 2-hydroxypropyl beta-cyclodextrin, further increased the su blingual bioavailability to 57.1%. The sublingual route may be an alternati ve route of administration of clomipramine, providing enhanced bioavailabil ity.