Wiedemann K, Holsboer F
Department of Psychiatry, University of Mainz, F.R.G.
Biol Psychiatry. 1987 Nov;22(11):1340-8. doi: 10.1016/0006-3223(87)90068-0.
We compared early biophase kinetics of dexamethasone in 33 patients with a major depression who received a DST either by an oral (n = 20) or an intravenous (n = 13) route. After an oral DST, the dexamethasone kinetics between 14 suppressors and 6 nonsuppressors were indistinguishable during the early distribution phase. However, elimination of dexamethasone from the circulation was significantly enhanced in DST nonsuppressors, resulting in an association of decreased plasma dexamethasone with elevated post-DST cortisol levels. Following intravenous DST administration, we identified 5 nonsuppressors and 8 suppressors whose plasma dexamethasone kinetics were indistinguishable, and during the elimination phase, were in the same order of magnitude as those of nonsuppressors after an oral DST. We suggest that the actual plasma concentration at the conventional post-DST sampling times does not reflect the biopotency of the test drug to suppress the pituitary adrenocortical activity. Plasma dexamethasone concentrations after an oral DST that were associated with nonsuppressed cortisol seem to be coherent phenomena of the underlying endocrine disturbance, the precise nature of which deserves further study.
我们比较了33例重度抑郁症患者中地塞米松的早期生物相动力学，这些患者通过口服（n = 20）或静脉注射（n = 13）途径接受地塞米松抑制试验（DST）。口服DST后，在早期分布阶段，14例抑制者和6例非抑制者之间的地塞米松动力学没有差异。然而，DST非抑制者体内地塞米松从循环中的消除显著增强，导致血浆地塞米松水平降低与DST后皮质醇水平升高相关。静脉注射DST后，我们识别出5例非抑制者和8例抑制者，他们的血浆地塞米松动力学没有差异，并且在消除阶段，其水平与口服DST后的非抑制者处于同一数量级。我们认为，在传统的DST采样时间的实际血浆浓度并不能反映试验药物抑制垂体肾上腺皮质活动的生物效能。口服DST后与未被抑制的皮质醇相关的血浆地塞米松浓度似乎是潜在内分泌紊乱的相关现象，其确切性质值得进一步研究。
