| Project/Area Number |
07672475
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
FURUTA Takashi Tokyo University of Pharmacy and Life Science, Pharmacy, Associate Professor, 薬学部, 助教授 (70120152)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBASAKI Hiromi Tokyo University of Pharmacy and Life Science, Pharmacy, Assistant, 薬学部, 助手 (20206121)
KASUYA Yasuji Tokyo University of Pharmacy and Life Science, Pharmacy, Professor, 薬学部, 教授 (90096686)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | _L-Histidine / Urocanic Acid / Histidine Ammonia-Lyase / Pharmacokinetics / In Vivo Enzyme Activities / Stable Isotopes / GC-MS / Metabolic Disorders / _L-ヒスチジン / 安定同位体標識体合成 / 同位体希釈質量分析 / 酵素反応 / 脱離反応 |
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| Research Abstract |
The pharmacokinetics of _L-histidine in human has been investigated to evaluate the in vivo histidine ammonia-lyase system for the conversion of _L-histidine to urocanic acid. Two healthy volunteers (subjects A and B) received a single 100-mg oral dose of _L-[3,3-^2H_2,1', 3'-^<15>N_2] histidine. Blood and urine samples were obtained over 24 hr after the administration and analyzed by stable isotope dilution mass spectrometry. The pharmacokinetic parameters were calculated based on a two-compartment model. The labeled _L-histidine in subject A (t_<1/2>=1.0hr) was eliminated approximately twice faster than that in subject B (t_<1/2>=1.9hr). The total body clearances (CL_T) were 70.0 liters/hr in subject A and 30.0 liters/hr in subject B.The low ratios of the renal clearance to the total body clearance (CL_<re>/CL_T ; 1.04% for subject A and 0.43% for subject B) indicated that most of _L-histidine was eliminated via the non-renal processes.
_L-Histidine was rapidly metabolized to urocanic acid. The maximum plasma concentrations of urocanic acid were 59.61 ng/ml at 30 min for subject A and 46.10 ng/ml at 60 min for subjectB.The slope of the plot of urinary excretion rate of urocanic acid vs.the plasma concentration of unchanged _L-histidine was demonstrated to reflect the metabolic clearance of _L-histidine to urocanic acid. The method of evaluating the in vivo human histidine ammonialyase activities discussed in this study offers a significant value with regard to the biochemical and clinical elucidations of the heterogeneity of histidinemia.
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