グルクロン酸抱合能に及ぼす抗てんかん薬多剤投与の影響

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Valproic acid (VPA) and phenytoin (PHT) are commonly used as antiepileptic drugs. They are metabolized by various pathways, and their metabolites are mainly excreted in the urine and bile. Studies on their metabolism in humans have been mainly performed after administration as a single drug but very few have been done for the case that these antiepileptic drugs are administered with each other. In this paper, we studied the effect of the co-administration of these drugs on their individual metabolism in humans. The concentrations of the antiepileptic drugs and their metabolites in urine and plasma were measured by liquid chromatography-mass spectrometry (LC-MS). In two patients administered only VPA as an antiepileptic agent, 60.9% of the dose (54.3%, 67.6%) was excreted as VPA-glucuronide (VPA-G). This result was similar to that reported in other papers. However, when VPA and PHT were co-administered in 5 patients, the excretion of VPA as VPA-G was 49.4±10.5% (mean±SD). This result was lower than that reported in other papers. VPA-G was detected in the blood of 2 of the five patients. The urinary excretion amounts of p-hydroxyphenyl-phenylhydantoin (p-HPPH), and PHPPH-G for the five patients given PHT as well as VPA were 2.0, 0.8, and 40.3%, respectively, of the amount of PHT administered. The urinary excretion percentage of p-HPPH-G was lower than that reported in other papers. These results indicate that the co-administration of VPA and PHT reciprocally inhibited each other's glucuronidation and reduced the urinary excretion percentage.
日本医療薬学会の論文
2006-07-10

グルクロン酸抱合能に及ぼす抗てんかん薬多剤投与の影響

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