Tornatore K M, Reed K, Venuto R C
Center for Clinical Pharmacy Research, School of Pharmacy, State University of New York, Buffalo.
J Med. 1993;24(2-3):98-112.
Circulating lymphocytes play a major role in mediating allograft rejection. The peripheral lymphocyte count is influenced by methylprednisolone administration, however, the relationship of methylprednisolone pharmacokinetics to lymphocyte trafficking patterns and its effect on selected lymphocyte subsets (CD4+, CD8+) in renal transplant recipients receiving chronic, fixed-doses of this glucocorticoid has not been studied. To examine this relationship, seven stable renal transplant recipients were given their usual oral methylprednisolone dose (mean daily dose = 15 mg) intravenously, and whole blood was obtained over 24 hr. CD4+ and CD8+ cells were quantitated with flow cytometry and serum concentrations of methylprednisolone were analyzed by high performance liquid chromatography (HPLC). Following methylprednisolone administration, a lymphocytopenia was noted in all patients with the CD4+ and CD8+ cells declining to less than 75% of baseline with a resultant nadir at 8 hr. The CD4+ and CD8+ count returned to baseline values by 12 to 24 hr in all patients. Interpatient variability in pharmacokinetic parameters of methylprednisolone was noted with a total body clearance of 240 +/- 112 mL/hr/Kg and half-life ranging from 2.2 to 3.9 hr. The variability seen in the clearance and distribution volume of methylprednisolone among these patients suggests that fixed doses result in a variable degree of systemic exposure. The poor correlation between methylprednisolone pharmacokinetic parameters and the decline of CD4+ and CD8+ cells indicates that other factors may play a role in the lymphocyte trafficking response. Nevertheless, nadir CD4+ and CD8+ cell counts may provide a measure of methylprednisolone immunosuppression in transplant recipients. Studies to examine their relationship to clinical outcomes (i.e., graft function, steroid toxicity, opportunistic infections) are currently in progress.
循环淋巴细胞在介导同种异体移植排斥反应中起主要作用。外周淋巴细胞计数受甲基强的松龙给药的影响，然而，在接受慢性固定剂量这种糖皮质激素的肾移植受者中，甲基强的松龙的药代动力学与淋巴细胞迁移模式的关系及其对选定淋巴细胞亚群（CD4 +、CD8 +）的影响尚未得到研究。为了研究这种关系，对7名稳定的肾移植受者静脉注射其常用口服甲基强的松龙剂量（平均每日剂量 = 15 mg），并在24小时内采集全血。通过流式细胞术对CD4 +和CD8 +细胞进行定量，并通过高效液相色谱法（HPLC）分析甲基强的松龙的血清浓度。给予甲基强的松龙后，所有患者均出现淋巴细胞减少，CD4 +和CD8 +细胞降至基线的75%以下，8小时时出现最低点。所有患者的CD4 +和CD8 +计数在12至24小时恢复到基线值。注意到甲基强的松龙药代动力学参数存在个体间差异，总体清除率为240±112 mL/hr/Kg，半衰期为2.2至3.9小时。这些患者中甲基强的松龙清除率和分布容积的差异表明，固定剂量会导致全身暴露程度不同。甲基强的松龙药代动力学参数与CD4 +和CD8 +细胞减少之间的相关性较差，表明其他因素可能在淋巴细胞迁移反应中起作用。然而，最低点CD4 +和CD8 +细胞计数可能提供肾移植受者中甲基强的松龙免疫抑制作用的一种衡量方法。目前正在进行研究以检查它们与临床结果（即移植肾功能、类固醇毒性、机会性感染）的关系。
