Retinal and systemic pharmacokinetics of the anti-inflammatory drug cloricromene following oral administration in the rat and rabbit.

Abstract

PURPOSE:

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.

• Authors: Claudio Bucolo, Francesco Maugeri, Adriana Maltese, Keith W Ward
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 23 Issue 3 Pg. 257-63 (Jun 2007) ISSN: 1080-7683 [Print] United States
• PMID: 17593009 (Publication Type: Journal Article)

Chemical References

• Platelet Aggregation Inhibitors
• Prodrugs
• cloricromen
• Chromonar

Topics

• Administration, Oral
• Animals
• Area Under Curve
• Chromatography, High Pressure Liquid
• Chromonar (administration & dosage, analogs & derivatives, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Stability
• Ischemia (drug therapy)
• Male
• Platelet Aggregation Inhibitors (administration & dosage, pharmacokinetics)
• Prodrugs (administration & dosage, pharmacokinetics)
• Rabbits
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Retina (drug effects, metabolism)
• Retinal Diseases (drug therapy)
• Species Specificity
• Tissue Distribution