title: 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.affiliation: Allergan, Inc Irvine, CA 92715, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Small
authors.forename: Andrew
authors.initials: A
authors.lastname: Acheampong
authors.forename: Brenda
authors.initials: B
authors.lastname: Reis
authors.forename: Katherine
authors.initials: K
authors.lastname: Stern
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.forename: Gregg
authors.initials: G
authors.lastname: Berdy
authors.forename: Randy
authors.initials: R
authors.lastname: Epstein
authors.forename: Robert
authors.initials: R
authors.lastname: Foerster
authors.forename: Lance
authors.initials: L
authors.lastname: Forstot
authors.forename: Diane D-S
authors.initials: DD
authors.lastname: Tang-Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D004311:Double-Blind Method; D004655:Emulsions; D005260:Female; D006801:Humans; D007322:Instillation, Drug; D007638:Keratoconjunctivitis Sicca / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D009883:Ophthalmic Solutions; D016572:Cyclosporine