Route of penetration of topically instilled nipradilol into the ipsilateral posterior retina.
OBJECTIVE
To investigate how topically instilled nipradilol penetrates the ipsilateral posterior retina-choroid in normal rabbit eyes.


METHODS
Albino rabbits were used. Topical instillation (1%, 100 microL) or intracameral (0.1%, 100 microL) or sub-Tenon injection (0.1%, 10 microL) of [(14)C]nipradilol was performed in one eye. Ocular and periocular distribution and the concentrations of [(14)C]nipradilol were determined by whole-head autoradiography, the results of which were validated by measurements in isolated tissues. In addition, the unchanged form of nonradiolabeled nipradilol in the posterior retina after topical instillation (1%, 100 microL) was quantified by liquid chromatography-tandem mass spectrometry (LC/MS/MS).


RESULTS
Autoradiography revealed that the nipradilol concentration after topical instillation was higher in the ipsilateral posterior retina-choroid than on the contralateral side (142.9 ng/g vs. 108.3 ng/g, P = 0.026), and in the periocular tissue around the optic nerve insertion on the ipsilateral side than on the contralateral side (207.1 ng/g vs. 141.1 ng/g, P < 0.001). After intracameral injection, radioactivity was observed only in anterior, but not posterior parts of the eye. Radioactivity was observed only in the ipsilateral posterior retina-choroid and periocular tissues around the optic nerve insertion after sub-Tenon injection. The results in the isolated tissues validated autoradiographic evaluations.


CONCLUSIONS
These results suggest that diffusion from posterior periocular tissues across the posterior sclera may be the main route for local penetration of the instilled drug to reach the posterior retina-choroid in albino rabbits.
Mizuno
Ken
K
Department of Pharmacology, Tokyo Research Laboratories, Kowa Co, Ltd, Tokyo, Japan.
Koide
Takashi
T
Shimada
Shunsuke
S
Mori
Junko
J
Sawanobori
Kimio
K
Araie
Makoto
M
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001345:Autoradiography; D001682:Biological Availability; D002829:Choroid / Q000378:metabolism*; D002853:Chromatography, Liquid; D004333:Drug Administration Routes; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D011412:Propanolamines; C036089:nipradilol