Rohatagi S, Hochhaus G, Mollmann H, Barth J, Galia E, Erdmann M, Sourgens H, Derendorf H
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, USA.
J Clin Pharmacol. 1995 Dec;35(12):1187-93. doi: 10.1002/j.1552-4604.1995.tb04045.x.
Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA after intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg) administration. Blood samples were collected at appropriate times over 24 hours, and TCA concentrations in plasma were measured by high-performance liquid chromatography and radioimmunoassay. Free drug concentrations were determined by ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lymphocytes, granulocytes, and cortisol. Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax model for lymphocytes and granulocytes. A novel linear release rate model was used to characterize the cortisol data. The E50 values determined from all three pharmacodynamic endpoints were not significantly different for the three treatments, indicating that these effects can be explained based on systemic steroid concentrations.
曲安奈德（TCA）是一种常用于治疗哮喘的皮质类固醇。吸入后，当吸入制剂被吞咽时，TCA可全身吸收，从而产生不良的全身效应。进行了一项临床研究，以确定静脉注射（2mg磷酸酯）、口服（5mg）和吸入（2mg）TCA后的全身副作用。在24小时内的适当时间采集血样，通过高效液相色谱法和放射免疫分析法测定血浆中的TCA浓度。通过超滤测定游离药物浓度，以关联药代动力学和药效学。TCA的游离分数（±标准差）为29.0±1.3%，且在高达1000ng/mL的研究浓度范围内与浓度无关。通过监测淋巴细胞、粒细胞和皮质醇来确定药效学参数。使用改良的Emax模型对淋巴细胞和粒细胞进行药代动力学/药效学建模。使用一种新型线性释放速率模型来表征皮质醇数据。从所有三个药效学终点确定的E50值在三种治疗中无显著差异，表明这些效应可以基于全身类固醇浓度来解释。
