Retinal and systemic pharmacokinetics of the anti-inflammatory drug cloricromene following oral administration in the rat and rabbit.
OBJECTIVE
The aim of this study was to evaluate the retina and plasma distribution of cloricromene, a coumarin derivative, and its active metabolite (MET) after an oral administration in rabbits and rats.


METHODS
A single dose of cloricromene was orally administered to rabbits (10 or 100 mg/kg) and to rats (100 mg/kg). Retina and plasma samples were collected at 15, 30, 60, and 90 min following administration. Drug concentrations in the retina and plasma were measured by high-performance liquid chromatography.


RESULTS
As anticipated, only the active metabolite was found in all samples. The retina and plasma showed the same T(max); peak levels of the drug were achieved at 15 min in rats and at 30 min in rabbits. In rabbits, MET exposure was approximately dose-proportional in both retina and plasma between the 10- and 100-mg/kg dose. Substantial retinal exposure was observed in both the rat and rabbit, at exposures approximately nine- to sixteenfold lower in the retina than in plasma.


CONCLUSIONS
The results showed that the active metabolite of cloricromene reached the retina after a single oral dose with exposures proportional to those in plasma. These data, along with the previously published potency data for cloricromene, suggest that cloricromene could be potentially useful in ischemic-retinal diseases where amelioration of blood flow and inflammation is desirable.
Bucolo
Claudio
C
Global Preclinical Development, Bausch & Lomb, Catania, Italy. bucocla@unict.it
Maugeri
Francesco
F
Maltese
Adriana
A
Ward
Keith W
KW
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D002866:Chromonar / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012164:Retinal Diseases / Q000188:drug therapy; D013045:Species Specificity; D014018:Tissue Distribution
D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; C025945:cloricromen; D002866:Chromonar