Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) were investigated in relation to sex and race in white males, black males, white females, and black females (n = 8/group) after a single oral dose (0.27 mg/kg) of prednisone. The study consisted of baseline and prednisone phases with 32-hour sampling in each phase. Women were studied during the luteal phase of their menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration, and pharmacokinetic data were analyzed by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T-helper, T-suppressor lymphocyte, and neutrophil cell counts were determined by FACS and hemocytometry, and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight-normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women, regardless of race (by 22% in whites and 40% in blacks for oral clearance, p < 0.01; by32% in whites and 38% in blacks for apparent volume of distribution, p < 0.01). The 50% inhibitory concentration (IC50) values for T-suppressor cell-trafficking inhibition were higher in whites than in blacks, regardless of sex (by 125% in men and 208% in women, p < 0.01). The IC50 or SC50 values for effects of prednisolone on cortisol secretion and T-helper lymphocyte or neutrophil trafficking were not statistically different between men and women, blacks and whites. The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race. However, these differences do not suggest the need for dosage adjustments, and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings.

译文

在单次口服剂量(0.27 mg / kg)的男性,白人男性,黑人男性,白人女性和黑人女性(n = 8 /组)中,研究了泼尼松龙的药代动力学(PK)和药效学(PD)与性别和种族的关系。强的松。该研究包括基线阶段和泼尼松阶段,每个阶段进行32小时采样。在月经周期的黄体期对妇女进行了研究。通过HPLC和超滤法测定血浆总泼尼松龙和游离血浆泼尼松龙的浓度,并使用WinNonlin通过区室拟合分析药代动力学数据。血浆皮质醇浓度通过HPLC测定。通过FACS和血细胞计数法测定T辅助细胞,T抑制淋巴细胞和中性粒细胞计数,并使用ADAPT II通过基本和扩展间接应答模型评估这些药效学数据。不论种族如何,男性的总体重标准化游离泼尼松龙口服清除率和表观分布量均高于女性(白人为22%,黑人为40%,黑人为40%,白人为32%,白人为38%)。表观分布体积中,%为黑色,p <0.01)。不论性别,白人的T抑制细胞贩运抑制作用的50%抑制浓度(IC50)值均高于黑人(男性为125%,女性为208%,p <0.01)。男性和女性,黑人和白人之间泼尼松龙对皮质醇分泌和T辅助淋巴细胞或中性粒细胞运输的影响的IC50或SC50值在统计学上无差异。这项研究的发现表明,泼尼松龙的PK / PD与性别和种族有关。但是,这些差异并不意味着需要调整剂量,还需要进行其他重复给药实验以全面评估这些发现的临床意义。

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