The influence of the absorption phase (the time of maximum blood concentration ; T
max) on the pharmacokinetics of cyclosporine (CYA) in the steady state after oral administration was studied in 26 renal transplant recipients. The patients were divided into three absorption phase groups with the T
max times as follows, group A (n=26) ; 0h⪈T
max<3h, group B (n=6) ; 3h⪈T
max<6h and group C (n=11) ; 6h⪈T
max<12h. CYA (dose ; 1.6-15.0 mg/kg/d) was administered orally to all 26 patients (10-52 years, 33.1-74.2 kg) every 12h. The blood specimens used in this study were collected just before administration (0h) in the morning and at intervals of 1, 2, 3, 6, 8 and 12h after administration. The whole blood CYA levels were measured by high-performance liquid chromatography (HPLC) or by fluorescence polarization immunoassay (FPIA) based on a specific monoclonal antibody. There were no significant differences between the three groups in terms of the dosage (mg/kg/d) and area-under-the-curve (AUC). The trough levels (0, 12h) correlated well to the AUC only in group A (r=0.842-0.907, p<0.001). The morning trough levels (0h) were significantly higher than the night trough levels (12h) in groups A and B (p<0.05-0.01). On the other hand, there was an excellent correlation between the maximal blood concentration (C
max) and the AUC of CYA in all three groups, 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 values is necessary for obtaining the most suitable therapeutic drug monitoring data of CYA with the patients who absorb slowly.
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