THE ESTIMATION OF THE PLASMA-FREE FRACTION OF CYCLOSPORINE IN RABBITSAND HEART-TRANSPLANT PATIENTS - THE APPLICATION OF A PHYSIOLOGICAL MODEL OF RENAL CLEARANCE
Ak. Shah et al., THE ESTIMATION OF THE PLASMA-FREE FRACTION OF CYCLOSPORINE IN RABBITSAND HEART-TRANSPLANT PATIENTS - THE APPLICATION OF A PHYSIOLOGICAL MODEL OF RENAL CLEARANCE, Biopharmaceutics & drug disposition, 16(1), 1995, pp. 59-70
We estimated the free fraction (f(u)) of cyclosporine (CyA) in the pla
sma from concentrations of CyA in urine (C-u) and plasma (C-p), urine
flow rate (UF), and glomerular filtration rate in rabbits and in heart
transplant patients. Following intravenous administration of CyA (5-3
0 mg kg(-1)) in ten NZW rabbits and oral administration of CyA (4.8-12
.1 mg kg(-1)) in nine heart transplant patients, CyA concentrations in
urine and plasma were measured by HPLC. The ratios of C-u to C-p and
UF data were fitted to a physiological model of renal clearance using
NONMEM. The free fraction of cyclosporine in the rabbits and the heart
transplant patients was 0.0122 and 0.14, respectively. Because of the
relatively law permeability of CyA across the tubular epithelium, no
apparent equilibrium between C-u and C-p at any urine flow rate was re
ached and, therefore, the C-u to C-p ratio will not be equal to f(u).