Pharmacokinetic studies of cortisol after oral administration of deuterium-labelled cortisol to a normal human subject.
Pharmacokinetic studies of cortisol after oral administration of deuterium-labelled cortisol to a normal human subject.
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正常人类受试者口服氘标记皮质醇后皮质醇的药代动力学研究。
DOI：
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发表时间：
1995
影响因子：
2
通讯作者：
T. Furuta
中科院分区：
文献类型：
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作者：
Y. Kasuya;M. Iwano;H. Shibasaki;T. Furuta
将微量（5mg）稳定同位素标记的皮质醇（[1,1,19,19,19- 2h5]皮质醇，皮质醇-d5）口服给健康受试者，以检测外源性皮质醇的药代动力学行为，并研究11 β -羟基类固醇脱氢酶（11 β - ohsd）催化皮质醇向可的松的相互转化。使用气相色谱/质谱方法可以同时测量内源性和外源性皮质醇和可的松的血浆浓度。给药量足够小，不会通过负反馈干扰或减少内源性皮质醇分泌。皮质醇-d5和可的松-d5的出现非常迅速。在给予皮质醇-d5后10分钟的血液样本中，检测到血浆浓度为154.8 ng ml-1皮质醇-d5和2.7 ng ml-1皮质醇-d5。皮质醇-d5在给药30 min后达到峰值196.6 ng ml-1。在给药后40 min，可的松-d5的峰值为15.5 ng ml-1，此后可的松-d5与可的松-d5的缓慢下降阶段平行下降。给药后4小时，皮质醇-d5和皮质醇-d5的血药浓度分别降至26.9 ng ml-1和4.6 ng ml-1。皮质醇-d5与皮质醇-d5的比值在给予皮质醇-d5 2小时后接近平台，此后达到约0.15的恒定值。可的松/皮质醇浓度比值（0.14-0.81，平均0.30）高于可的松-d5/可的松-d5比值，这可能提供了可的松可能不仅通过皮质醇转化途径形成，还通过其他生物转化过程形成的可能性的重要信息。
A trace amount (5 mg) of stable isotopically labelled cortisol ([1,1,19,19,19-2H5]cortisol, cortisol-d5) was administered orally to a healthy human subject to examine the pharmacokinetic behaviour of exogenous cortisol and study the interconversion of cortisol to cortisone catalysed by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The use of a gas chromatographic/mass spectrometric method allowed the simultaneous measurement of the plasma concentrations of endogenous and exogenous cortisol and cortisone. The amount administered was sufficiently small not to disturb or decrease the endogenous cortisol secretion by negative feedback. The appearance of cortisol-d5 and cortisone-d5 was very rapid. In a blood sample taken 10 min after administration of cortisol-d5, plasma concentrations of 154.8 ng ml-1 cortisol-d5 and 2.7 ng ml-1 cortisone-d5 were detected. A peak value of 196.6 ng ml-1 cortisol-d5 was observed 30 min after cortisol-d5 administration. The peak value of cortisone-d5 was 15.5 ng ml-1 40 min after cortisol-d5 administration, and thereafter cortisone-d5 declined in parallel with the slower decline phase of cortisol-d5. The plasma concentrations fell as low as 26.9 ng ml-1 for cortisol-d5 and 4.6 ng ml-1 for cortisone-d5 4 h after cortisol-d5 administration. The ratio of cortisone-d5 to cortisol-d5 approached a plateau 2 h after cortisol-d5 administration, reaching a constant value of approximately 0.15 thereafter. The higher value of the cortisone/cortisol concentration ratio (0.14-0.81; average 0.30) than the cortisone-d5/cortisol-d5 ratio may provide important information about the possibility that cortisone might be formed not only via the pathway of the cortisol conversion but also through other biotransformation processes.