Tissue distribution of moxaverine-hydrochloride in the rabbit eye and plasma.
OBJECTIVE
The aim of this study was to determine the tissue distribution and epithelial penetration of moxaverine-hydrochloride (MOX) in the rabbit eye.


METHODS
For systemic application, a radioactively labeled MOX solution was injected into the ear vein of Dutch-belted pigmented male rabbits. For topical dosing, an identical solution was administered. At predetermined time points, rabbits were sacrificed, the eyes dissected, and the amount of MOX in the ocular tissues measured. To examine the MOX permeability across the corneal epithelium, transport studies using rabbit corneal epithelial cell culture were conducted and the respective apparent permeability coefficient in absorptive (a to b) or secretive (b to a) direction was calculated.


RESULTS
Topical delivery resulted in high concentrations of MOX in the cornea and conjunctiva, although other tissues of the anterior part yielded lower MOX concentrations. In the tissues of the posterior part, high amounts were detected in the retina. Plasma levels were low. The apparent permeability coefficient across corneal epithelial cell layers was in the range of 10(5) cm/s, exhibiting no apparent directionality.


CONCLUSIONS
A topical dosing of MOX to posterior regions of the eye seems feasible. MOX levels in the posterior part of the eye were remarkably high, without causing stringent plasma levels. The high apparent permeability coefficient of MOX across the corneal epithelial cell layers might be caused by the lipophilic nature of the drug and was in the range of other compounds with comparable physicochemical properties.
Becker
Ulrich
U
Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbrücken, Germany.
Ehrhardt
Carsten
C
Schaefer
Ulrich F
UF
Gukasyan
Hovhannes J
HJ
Kim
Kwang-Jin
KJ
Lee
Vincent H L
VH
Lehr
Claus-Michael
CM
D000818:Animals; D001682:Biological Availability; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D007275:Injections, Intravenous; D007322:Instillation, Drug; D008297:Male; D010208:Papaverine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D014018:Tissue Distribution
D010208:Papaverine; C004490:moxaverine