Ritchie J C, Belkin B M, Krishnan K R, Nemeroff C B, Carroll B J
Department of Psychiatry, Duke University, Durham, NC 27710.
Biol Psychiatry. 1990 Jan 15;27(2):159-73. doi: 10.1016/0006-3223(90)90646-j.
Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.
地塞米松（dex）生物利用度的改变或药代动力学的改变可能导致精神科患者地塞米松抑制试验（DST）呈阳性。我们测量了32例原发性重度抑郁症（MDD）患者、14例其他精神障碍患者和16名正常对照者的血浆dex和血浆皮质醇浓度。皮质醇通过竞争性蛋白结合（CPB）法测量，dex通过放射免疫分析（RIA，IgG Corp.）测量。此外，为了验证这种方法在DST中的应用，我们还使用雅培TDx分析仪上的荧光偏振免疫分析（FPIA）测量了皮质醇。FPIA和CPB皮质醇结果之间的一致性非常好。根据定义，抑郁非抑制者在服用dex后上午8点、下午3点和晚上10点的平均血浆皮质醇浓度显著高于抑郁抑制者、精神科对照者和正常志愿者。当比较DST非抑制者和抑制者时，无论诊断组如何，DST非抑制者的血浆dex浓度显著较低（p<0.01）。上午8点时，所有受试者的血浆皮质醇水平与血浆dex水平之间存在显著负相关（r = -0.365，n = 44，p<0.05）。当按诊断类别对受试者进行分类时，抑郁性非抑制者与抑郁性抑制者之间以及精神科对照非抑制者与相应抑制者组之间存在强烈但无统计学意义的趋势，即血浆dex浓度较低。当我们将分析限制在经验得出的血浆dex浓度的中间范围内（在此范围内DST结果被认为是有效的）时，这些关系消失了。我们得出结论，dex的生物利用度或药代动力学可能对DST结果有显著影响。需要进一步研究以确定dex及其代谢产物的定量以及在DST期间的特定时间点进行测定是否会提高DST在精神科患者中的预测或解释价值。
