EFFECT OF CYTOCHROME-P450 INDUCTION ON PHOSPHORUS METABOLITES AND PROTON RELAXATION-TIMES MEASURED BY IN-VIVO P-31-MAGNETIC RESONANCE SPECTROSCOPY AND H-1-MAGNETIC RESONANCE RELAXOMETRY IN HUMAN LIVER

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by P-31 magnetic resonance (MR) spectro scopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic s tudies in humans are lacking, Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented ind uction of oxidative metabolism as measured by an increase in urinary 6 -beta-hydroxycortisol output in all volunteers (P = .0004). P-31-MR sp ectroscopy and H-1-MR relaxometry were performed before and after hepa tic P450 induction, As shown by P-31-MR spectroscopy the median phosph omonoester concentration (PME) relative to nucleoside triphosphate (NT P) 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 phosp hodiesters (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). A n increase in the level of inorganic phosphates (Pi) relative to NTP w as observed, but changes were not significant, As shown by H-1-MR rela xometry, a nonsignificant trend of the liver parenchyma to shorter rel axation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo P-31-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with P-31-MR spectroscopy must take into account the potential effects of P450-inducing agents.