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 beta-cyclodextrin, further increased the sublingual bioavailability to 57.1%. The sublingual route may be an alternative route of administration of clomipramine, providing enhanced bioavailability.
Yoo
S D
SD
College of Pharmacy, SungKyunKwan University, 300 Chonchon-dong, Jangan-ku, Suwon City, 440-746, Korea.
Yoon
B M
BM
Lee
H S
HS
Lee
K C
KC
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000286:Administration, Sublingual; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002463:Cell Membrane Permeability / Q000187:drug effects; D002997:Clomipramine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003505:Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007552:Isotonic Solutions; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage; D047392:beta-Cyclodextrins
D000929:Antidepressive Agents, Tricyclic; D003505:Cyclodextrins; D007552:Isotonic Solutions; D014677:Pharmaceutical Vehicles; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D012965:Sodium Chloride; D002997:Clomipramine