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) administration. The mean oral bioavailability of clomipramine was 24.8% and 29.7%, respectively, in conscious rats and in rats anesthetized with ketamine/xylazine (30/3 mg/kg). When given sublingually in isotonic saline at a dose of 50 mg/kg, clomipramine was rapidly absorbed, and the mean absolute bioavailability (36.2%) was increased over oral dosing. The mean AUC values of clomipramine were 2258 ± 1762 ng·h/mL and 1891 ± 867 ng·h/mL after oral administration to conscious and anesthetized rats, respectively, and 3303 ± 1576 ng·h/mL after sublingual administration to anesthetized rats. Sublingual administration (5 mg/kg doses) of clomipramine formulated with a permeation enhancer, 2-hydroxypropyl β-cyclodextrin, further increased the sublingual bioavailability to 57.1%. The sublingual route may be an alternative route of administration of clomipramine, providing enhanced bioavailability.