Increased bioavailability of clomipramine after sublingual administration in rats

• Published in: Journal of pharmaceutical sciences Vol. 88; no. 11; pp. 1119 - 1121
• Main Authors: Yoo, Sun Dong, Yoon, Byung Mun, Lee, Hye Suk, Lee, Kang Choon
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.11.1999; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Administration, Sublingual; Animals; Antidepressive Agents, Tricyclic - administration & dosage; Antidepressive Agents, Tricyclic - blood; Antidepressive Agents, Tricyclic - pharmacokinetics; beta-Cyclodextrins; Biological and medical sciences; Biological Availability; Cell Membrane Permeability - drug effects; Clomipramine - administration & dosage; Clomipramine - blood; Clomipramine - pharmacokinetics; Cyclodextrins - administration & dosage; Cyclodextrins - pharmacology; Dose-Response Relationship, Drug; Injections, Intravenous; Intestinal Absorption; Isotonic Solutions; Male; Medical sciences; Mouth Mucosa - metabolism; Neuropharmacology; Pharmaceutical Vehicles - administration & dosage; Pharmaceutical Vehicles - pharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Sodium Chloride - administration & dosage; Intravenous administration; Rat; Psychotropic; Rodentia; Oral administration; Sublingual administration; Bioavailability; Clomipramine; Tricyclic compound; Blood; Blood plasma; Vertebrata; Mammalia; Animal; Antidepressant agent; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js990163p

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 bioavail-ability (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.