Single-dose response kinetics of cyclosporine. 1987

F Bozkurt, and H Stierle, and P Schollmeyer, and E Keller

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011863 Radioimmunoassay Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. Radioimmunoassays
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003524 Cyclosporins A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. Cyclosporines
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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