CYCLOSPORINE LEVEL IN BLOOD AS MONITORED BY AREA-UNDER-THE-CURVE (AUC) .3. THE INFLUENCE OF ABSORPTION PHASE AFTER ORALLY DOSING

The influence of the absorption phase (the time of maximum blood conce ntration; T-max) on the pharmacokinetics of cyclosporine (CYA) in the steady state after oral administration was studied in 26 renal transpl ant recipients. The patients were divided into three absorption phase groups with the T-max times as follows, group A (n = 26); 0 h less tha n or equal to T-max < 3 h, group B (n = 6); 3 h less than or equal to T-max < 6 h and group C (n = 11); 6 h less than or equal to T(max)less than or equal to 12 h. CYA (dose; 1.6-15.0 mg/kg/d) was administered orally to all 26 patients (10-52 years, 33.1-74.2kg) every 12 h. The b lood specimens used in this study were collected just before administr ation (0 h) in the morning and at intervals of 1, 2, 3, 6, 8 and 12 h after administration. The whole blood CYA levels were measured by high -performance liquid chromatography (HPLC) or by fluorescence polarizat ion immunoassay (FPIA) based on a specific monoclonal antibody. There were no significant differences between the three groups in terms of t he dosage (mg/kg/d) and area-under-the-curve (AUC). The trough levels (0, 12 h) correlated well to the AUC only in group A (r = 0.842-0.907, p < 0.001). The morning trough levels (0 h) were significantly higher than the night trough levels (12 h) in groups A and B (p < 0.05-0.01) . On the other hand, there was an excellent correlation between the ma ximal blood concentration (C-max) and the AUC of CYA in all three grou ps, although the C-max of group C was significantly less than that of group A (p < 0.05). Moreover, it was impossible to estimate the T-max of each individual patient prior to the collection of blood specimens because the T-max values after oral dosing of CYA varied greatly from patient to patient. This suggests that the monitoring of the AUC value s is necessary for obtaining the most suitable therapeutic drug monito ring data of CYA with the patients who absorb slowly.