Taylor A, Bikle D D, Norman M E
Metabolic Bone Disease Laboratory, Alfred I. duPont Institute, Wilmington, Delaware 19899.
J Clin Endocrinol Metab. 1988 Jul;67(1):198-202. doi: 10.1210/jcem-67-1-198.
Dihydrotachysterol (DHT2) has been a safe and effective treatment for hypocalcemic disorders for many years, but few assays for quantitation of DHT2 have been developed. Thus little is known about its pharmacokinetics. The 2-fold purpose of this study was 1) to develop a practical method for quantitating DHT2 after oral dosing in normal subjects, and 2) to assess changes in serum DHT2 levels and calcium and phosphorus metabolism after DHT2 administration for 8 days. Peak serum DHT2 levels in six normal subjects, assayed by high performance liquid chromatography were achieved 4 h after administration of 0.4-0.8 mg DHT2; at 24 h, levels had declined by 70% whether DHT2 had been given for 1 or 8 days. These data indicate that a standard approach is needed to interpret the results of serum DHT2 measurements in treated patients. Interfering substances were detected in lipemic serum. The major biological effects of DHT2 administration were hypercalciuria in two subjects and a fall in serum 1,25-dihydroxyvitamin D[1,25-(OH)2D] levels, including free levels when measured, in all subjects. Possible explanations for this fall in serum 1,25-(OH)2D levels include decreased 1,25-(OH)2D production because of competition for the 1 alpha-hydroxylase enzyme by a metabolite(s) of DHT or increased metabolic clearance of 1,25-(OH)2D.
多年来，双氢速甾醇（DHT2）一直是治疗低钙血症的一种安全有效的药物，但用于定量DHT2的检测方法却很少。因此，人们对其药代动力学了解甚少。本研究的双重目的是：1）建立一种实用的方法来定量正常受试者口服给药后的DHT2；2）评估DHT2给药8天后血清DHT2水平以及钙和磷代谢的变化。通过高效液相色谱法检测，6名正常受试者在服用0.4 - 0.8 mg DHT2后4小时达到血清DHT2峰值水平；在24小时时，无论DHT2给药1天还是8天，水平均下降了70%。这些数据表明，需要一种标准方法来解释治疗患者血清DHT2测量结果。在高脂血症血清中检测到干扰物质。给予DHT2的主要生物学效应是两名受试者出现高钙尿症，所有受试者血清1,25 - 二羟维生素D[1,25-(OH)2D]水平下降，包括测量的游离水平。血清1,25-(OH)2D水平下降的可能解释包括由于DHT的代谢产物与1α - 羟化酶竞争导致1,25-(OH)2D生成减少，或1,25-(OH)2D的代谢清除增加。
