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.
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 [14C]diazepam, L-3,4-dihydroxyphenyL[3-(14)C]alanine or [14C]inulin was administered on the day following the surgical operation to avoid the influence of anesthesia. Radioactive concentrations of [14C]DOPA decreased rapidly in the first 1 min, then decreased gradually. The concentrations of [14C]diazepam increased within the first 1 min and then decreased gradually. The concentration of [14C]inulin was approximately 10 times higher than that of [14C]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 [14C]diazepam and [14C]DOPA were detected as early as 5 s after administration. These results suggest that the in vivo hepatic first pass effect of drugs in the early period of injection (5 s) can be studied using these techniques.
Nishigaki
J
J
Institute of Whole Body Metabolism, Inba, Chiba, Japan.
Suzuki
Y
Y
Shigematsu
A
A
D000818:Animals; D002250:Carbon Radioisotopes / Q000097:blood; D002406:Catheterization, Peripheral; D003975:Diazepam / Q000097:blood / Q000493:pharmacokinetics*; D004298:Dopamine / Q000097:blood; D007444:Inulin / Q000097:blood / Q000493:pharmacokinetics*; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood / Q000493:pharmacokinetics*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D002250:Carbon Radioisotopes; D018377:Neurotransmitter Agents; D007980:Levodopa; D007444:Inulin; D003975:Diazepam; D004298:Dopamine; D009638:Norepinephrine