Block W, Reichel C, Träber F, Skodra T, Lamerichs R, Kreft B, Spengler U, Sauerbruch T, Schild H H
Department of Radiology, University of Bonn, Germany.
Hepatology. 1997 Dec;26(6):1587-91. doi: 10.1002/hep.510260629.
Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.
通过31P磁共振（MR）波谱获得的磷酸二酯信号可能是苯巴比妥或乙醇诱导肝脏氧化代谢（P450诱导）的一种特异性标志物。目前尚缺乏针对人类的系统性研究。因此，我们对10名志愿者进行了研究，这些志愿者接受利福平（600mg/天）治疗6天，结果显示所有志愿者的尿6-β-羟基皮质醇排出量增加，这证明了氧化代谢被诱导（P = 0.0004）。在肝脏P450诱导前后分别进行了31P-MR波谱和1H-MR弛豫测量。如31P-MR波谱所示，相对于核苷三磷酸（NTP）的磷酸单酯浓度（PME）中位数从诱导前的0.63（范围为0.40 - 0.89）增加到诱导后的0.76（0.49 - 1.67），增幅为21%（P = 0.0451）。相对于NTP的磷酸二酯（PDE）中位数水平从诱导前的4.82（3.41 - 6.67）增加到诱导后的6.18（4.63 - 11.63），增幅为28%（P = 0.0091）。观察到相对于NTP的无机磷酸盐（Pi）水平有所增加，但变化不显著。如1H-MR弛豫测量所示，P - 450诱导后肝脏实质的弛豫时间有缩短的趋势，但不显著。总之，利福平诱导肝脏后，PME/NTP和PDE/NTP比值（通过体内31P-MR波谱测量）均显著增加。使用31P-MR波谱进行的进一步临床研究必须考虑P450诱导剂的潜在影响。
