Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration.
OBJECTIVE
To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases.


METHODS
Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS).


RESULTS
There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples.


CONCLUSIONS
LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake.
Mora
Paolo
P
Institute of Ophthalmology, University of Parma, Via Gramsci 14, 43100 Parma, Italy. paolo.mora@unipr.it
Ceglarek
Uta
U
Manzotti
Francesca
F
Zavota
Laura
L
Carta
Arturo
A
Aldigeri
Raffaella
R
Orsoni
Jelka G
JG
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000188:drug therapy; D002387:Cataract Extraction; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007903:Lens Capsule, Crystalline / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000378:metabolism*; D014605:Uveitis / Q000378:metabolism*
D007166:Immunosuppressive Agents; D016572:Cyclosporine