Iwahori T, Takeuchi H, Matsuno N, Johjima Y, Konno O, Nakamura Y, Hama K, Uchiyama M, Ashizawa T, Okuyama K, Nagao T, Abudoshukur M, Hirano T, Oka K
The Fifth Surgery, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
Transplant Proc. 2005 May;37(4):1739-40. doi: 10.1016/j.transproceed.2005.02.104.
We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.
我们对环孢素（NEO）和他克莫司（TAC）的血药浓度进行了24小时监测，评估药代动力学参数并描述昼夜变化特征。对9例服用NEO的患者进行了10次监测，对11例服用TAC的患者中的12例进行了监测。所有病例均每日口服两次等量药物。在早晨和晚上服用NEO或TAC之前以及之后1、2、3、4、6和12小时采集血样。比较了两种药物在早晨和晚上给药时的药代动力学参数。与早晨给药相比，晚上服用NEO和TAC时，AUC0-12、AUC0-4、C(max)、C2和C(max)/C(min)显著降低。晚上的C(min)值显著更高。NEO的T(max)在晚上更长，尽管没有显著差异；TAC的T(max)在晚上显著更长。我们发现，与早晨给药相比，晚上服用NEO和TAC会导致生物利用度降低和吸收延迟。据认为，由于TAC的峰值水平较低且血药浓度曲线比NEO更平坦，因此早晨和晚上给药之间的生物利用度差异较小。由于吸收延迟，晚上给药后的C(min)高于早晨，尽管两种药物的生物利用度在晚上均降低。这些结果表明，我们必须认识到明显较高的谷值水平。
