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Single-dose response kinetics of cyclosporine.

Authors
Type
Published Article
Journal
Clinical Nephrology
0301-0430
Publisher
Dustri-Verlag Dr. Karl Feistle
Publication Date
Volume
28
Issue
1
Pages
10–14
Identifiers
PMID: 3304744
Source
Medline
License
Unknown

Abstract

Cyclosporine (Cy) dose-response kinetics were studied in 8 renal failure patients awaiting kidney transplantation. All patients received a single oral dose of Cy (7 mg/kg). Blood samples were drawn frequently before and until 4 days after Cy administration. Cy blood levels were measured by radioimmunoassay (RIA). OKT3-induced in vitro proliferation of simultaneously isolated lymphocytes was determined by H3-thymidine incorporation. T cell subpopulations were enumerated using a peroxidase-antiperoxidase method. Mean Cy blood level reached its peak (Cmax = 1,466 +/- 186 ng/ml) at 4 to 6 hours, the elimination half life (t1/2) measured 31 +/- 7.2 hours. The T4/T8 cell ratio did not change during the study, the total numbers of T3, T4 and T8 positive lymphocytes showed well known circadian variations without an apparent influence of Cy. There was a strong relationship between Cy blood levels and the inhibition of in vitro lymphocyte proliferation (y = 21.1 -0.007x, r = -0.91, p less than 0.001). With decreasing Cy blood concentrations the proliferative potency of lymphocytes was restored without delay in time. In conclusion circulating T cell subpopulations are not influenced by a single dose of Cy, the strong correlation between drug levels and the inhibition of lymphoproliferation suggest that RIA derived Cy blood concentrations are a valuable tool for estimating immunosuppression.

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