OBJECTIVE: The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects. METHODS: In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake. RESULTS: Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P<0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P<0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P<0.01), although CsA doses and concentrations were not different between these two groups. CONCLUSION: We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.
OBJECTIVE: The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects. METHODS: In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake. RESULTS: Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P<0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P<0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P<0.01), although CsA doses and concentrations were not different between these two groups. CONCLUSION: We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.
Authors: F O'Valle; F L Mesa; M Gómez-Morales; D Aguilar; M D Caracuel; M T Medina-Cano; M Andújar; J López-Hidalgo; R García del Moral Journal: J Periodontol Date: 1994-07 Impact factor: 6.993