Shah A K, Brundage R C, Lake K D, Sawchuk R J
Marion Merrell Dow Inc., MO 64134-0627, USA.
Biopharm Drug Dispos. 1995 Jan;16(1):59-70. doi: 10.1002/bdd.2510160106.
We estimated the free fraction (fu) of cyclosporine (CyA) in the plasma from concentrations of CyA in urine (Cu) and plasma (Cp), urine flow rate (UF), and glomerular filtration rate in rabbits and in heart transplant patients. Following intravenous administration of CyA (5-30 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 Cu to Cp 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 low permeability of CyA across the tubular epithelium, no apparent equilibrium between Cu and Cp at any urine flow rate was reached and, therefore, the Cu to Cp ratio will not be equal to fu.
我们根据兔和心脏移植患者尿液中环孢素（CyA）浓度（Cu）、血浆中环孢素浓度（Cp）、尿流率（UF）以及肾小球滤过率，估算了血浆中环孢素的游离分数（fu）。给10只新西兰白兔静脉注射环孢素（5 - 30 mg kg⁻¹），给9名心脏移植患者口服环孢素（4.8 - 12.1 mg kg⁻¹）后，用高效液相色谱法测定尿液和血浆中的环孢素浓度。将Cu与Cp的比值以及UF数据用NONMEM软件拟合到肾脏清除的生理模型中。兔和心脏移植患者中环孢素的游离分数分别为0.0122和0.14。由于环孢素穿过肾小管上皮的通透性相对较低，在任何尿流率下Cu与Cp之间均未达到明显平衡，因此，Cu与Cp的比值不等于fu。
