Cyclosporine use in miscellaneous clinical settings other than organ transplantations: is there any evidence for target levels?
BACKGROUND
Cyclosporine, once a corner stone in organ transplantation for decades, its use is expanded to treat several autoimmune conditions despite lacking profound evidence for its advantages. The aim of the retrospective study was to evaluate differences in trough blood levels of cyclosporine in some clinical indications other than transplantation.


METHODS
Blood cyclosporine trough levels determined by fluorescent polarization immunoassay (FPIA) TDx Abbott Diagnostics for TDM purpose in one year period was pooled from laboratory data-base. Total of 304 levels from 45 patients (26 males: 19 females) aged 2-62 years, who were on oral cyclosporine daily maintenance dose for conditions like systemic lupus erythematosus (SLE), atopic dermatitis (ADS), idiopathic thrombocytopenic purpura (ITP), dermatopolymyositis (DMS), and cardiomyopathy (CMP) were included.


RESULTS
Cyclosporine trough was undetectable in 27 occasions, with maximum1213 microg/L, mode 74 ug/L, median 91 ug/L, mean 104.4+/-119.5 ug/L SD, and SE 6.85 respectively. Despite poorly de fi ned target, most clinicians desired trough concentrations not exceeding 100 microg/L, aiming to reduce toxicity. In this respect, nearly 35% were above this point, whereas 8% were below the detection limit of the method. There were no significant differences in concentrations within diagnostic groups except for ADS versus ITP (p<0.0039).


CONCLUSIONS
Extended use of cyclosporine in several autoimmune diseases is promising. However, no evidence-based target levels in miscellaneous indications. Studies are needed to demonstrate overall benefits of CSA in relation to trough level and dynamic indicators (biomarkers) like expression of IL-2 and its receptor as targeted cell products in the future.
Tesfaye
Hundie
H
Department of Clinical Biochemistry and Pathobiochemistry, Division of Clinical Pharmacology, Charles University, Czech Republic.
Prusa
Richard
R
Jedlickova
Blanka
B
Segethova
Jitka
J
D000293:Adolescent; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D003876:Dermatitis, Atopic / Q000188:drug therapy; D003882:Dermatomyositis / Q000188:drug therapy; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy; D014181:Transplantation Immunology; D055815:Young Adult
D016572:Cyclosporine