Division of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, UK.
Br J Clin Pharmacol. 2012 Sep;74(3):456-64. doi: 10.1111/j.1365-2125.2012.04210.x.
Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP).
Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 µg BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10,100 µg inhalations from a Qvar(®) Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 µg inhalations from a Clenil(®) pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone-17-monopropionate (17-BMP) and beclometasone (BOH) were measured.
No BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %.
The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies.
已经确定了尿药动力学方法来确定吸入后肺和全身相对生物利用度。我们已经将这种方法扩展到吸入用丙酸倍氯米松（BDP）。
获得伦理委员会批准，所有受试者均同意。12 名健康志愿者随机接受了 2000µg BDP 溶液（OralC）和不接受（Oral）5g 口服活性炭、10,100µg 从 Qvar® Easibreathe 计量吸入器（pMDI）（QvarC）和不接受（Qvar）口服活性炭和 8 次 250µg 从 Clenil®pMDI（Clenil）吸入的剂量，每个剂量间隔>7 天。受试者在研究剂量后 0、0.5、1、2、3、5、8、12 和 24 小时提供尿液样本。测量尿液中 BDP 及其代谢物，丙酸倍氯米松-17-单丙酸酯（17-BMP）和倍氯米松（BOH）的浓度。
OralC 给药后，在任何样本中均未检测到 BDP、17-BMP 或 BOH。口服后，所有尿液样本中均未检测到 BDP，在前 30 分钟内未排泄 17-BMP 或 BOH。与 Oral 相比，在 Qvar 和 Clenil 后第 30 分钟和 24 小时累积尿排泄中，显著更多（P<0.001）的 BDP、17-BMP 和 BOH。Qvar 与 Clenil 相比，30 分钟尿排泄的平均比值（90%置信区间）为 231.4（209.6，255.7）%。
使用 30 分钟和 24 小时累积吸入后样本，测定吸入后肺和全身相对生物利用度的尿药代动力学方法适用于 BDP。Qvar 与 Clenil 的比值与相关的临床和肺部沉积研究一致。
