Blood concentrations of cyclosporin a during long-term treatment with cyclosporin a ophthalmic emulsions in patients with moderate to severe dry eye disease.

Abstract

To quantify blood cyclosporin A (CsA) concentrations during treatment with CsA topical ophthalmic emulsions, blood was collected from 128 patients enrolled in a Phase 3, multicenter, double-masked, randomized, parallel-group study of CsA eyedrops for treatment of moderate to severe dry eye disease. Patients received 0.05% CsA, 0.1% CsA, or vehicle b.i.d. for 6 months; vehicle-treated patients then crossed over to 0.1% CsA b.i.d. for 6 months. CsA concentrations were measured using a validated LC/MS-MS assay (quantitation limit = 0.1 ng/mL). No patient receiving 0.05% CsA had any quantifiable CsA in the blood (n = 96 samples). All but 7 of 128 (5.5%) trough blood samples from the 0.1% CsA group were below the quantitation limit for CsA; none exceeded 0.3 ng/mL. CsA was also below the limit of quantitation in 205 of 208 (98.6%) of serial postdose blood samples collected from 26 patients during 1 dosing interval between months 9 and 12. The highest C(max) measured, 0.105 ng/mL at 3 hours postdose, occurred in a 0.1% CsA-treated patient. These results indicate that long-term use of topical CsA ophthalmic emulsions at doses that are clinically efficacious for treating dry eye will not cause any system-wide effects.

• Authors: David S Small, Andrew Acheampong, Brenda Reis, Katherine Stern, William Stewart, Gregg Berdy, Randy Epstein, Robert Foerster, Lance Forstot, Diane D-S Tang-Liu
• Journal: Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics (J Ocul Pharmacol Ther) Vol. 18 Issue 5 Pg. 411-8 (Oct 2002) ISSN: 1080-7683 [Print] United States
• PMID: 12419092 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Emulsions
• Ophthalmic Solutions
• Cyclosporine

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, blood, therapeutic use)
• Area Under Curve
• Chromatography, High Pressure Liquid
• Cyclosporine (administration & dosage, blood, therapeutic use)
• Double-Blind Method
• Emulsions
• Female
• Humans
• Instillation, Drug
• Keratoconjunctivitis Sicca (blood, drug therapy)
• Male
• Middle Aged
• Ophthalmic Solutions