A Novel Method for Measuring the Hepatic First-Pass Effect and Metabolic Rate of L-3,4-Dihydroxyphenylalanine (DOPA), Diazepam and Inulin in Rat Liver.

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A method to analyze in vivo metabolites in blood obtained from the hepatic vein after the intraportal injection of a drug was established. This method includes cannulation into the portal vein, hepatic vein and bile duct, followed by TLC-autoradioluminography of a non-extracted sample.Either [^<14>C]diazepam, L-3,4-dihydroxyphenyl[3-^<14>C]alanine or [^<14>C]inulin was administered on the day following the surgical operation to avoid the influence of anesthesia. Radioactive concentrations of [^<14>C]DOPA decreased rapidly in the first 1 min, then decreased gradually. The concentrations of [^<14>C]diazepam increased within the first 1 min and then decreased gradually. The concentration of [^<14>C]inulin was approximately 10 times higher than that of [^<14>C]DOPA, and both decreased gradually. These results show that the uptake levels of the drugs to the liver varied depending on the drugs. The metabolites of [^<14>C]diazepam and [^<14>C]DOPA were detected as early as 5s after administration. These results suggest that the in vivo hepatic first pass effect of drugs in the early period of injection (5s) can be studied using these techniques.
社団法人日本薬学会の論文
1998-07-15