Assessment of liver metabolic function in women (For an optimal dosage regimen)

• Project/Area Number: 07672466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 応用薬理学・医療系薬学
• Research Institution: Oita Medical University
• Principal Investigator: KOTEGAWA Kimiko Oita Medical University Dept.of Clinical Pharmacology and Therapeutics, 医学部・臨床薬理, 文部技官 (20244171)
• Co-Investigator(Kenkyū-buntansha): KOTEGAWA Tsutomu Oita Medical University Dept.of Clinical Pharmacology and Therapeutics Assistant, 医学部, 助手 (20264343) ; NAKANO Shigeyuki Oita Medical University Dept.of Clinical Pharmacology and Therapeutics Professor, 医学部, 教授 (10033341)
• Project Period (FY): 1995 – 1996
• Project Status: Completed (Fiscal Year 1996)
• Budget Amount: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: liver metabolic function / caffeine / women / menstrual cycle / pregnancy / 薬物代謝

Research Abstract

We investigated the effect of menstrual cycle and pregnancy on liver metabolic function. The protocol was approved by the institutional review board of Oita Medical University for clinical trials. The caffeine test was utilized to the assessment of liver metabolic function. The subjects were 12 healthy women with regular menstrual cycles. The study was performed at four stages in the menstrual cycle (Phase I : 2-4 days after the onset of menses, Phase II : 13-15 days after the onset of menses, Phase III : 7-5 days from the onset of next menses, Phase IV : 4-1 days from the onset of next menses). Each subject received a capsule of caffeine 150mg. We also investigated the metabolism of caffeine in a group of 13 pregnant women (Phase I : 3-4 months gestation, Phase II : 6-7 months, Phase III : 9-10 months, Phase IV : about 1 month post partum). Pregnant women was given a caffeine containing beverage (tea or coffee) and the activities of several enzymes [cytochrome P450 1A2 (CYP1A2), xanth ine oxidase (XO), N-acetyl-transferase (NAT)] were assessed by the urinary molar concentration ratios of caffeine metabolites. The concentrations of metabolites (AFMU,1-methylxanthin, 1-methyluric acid, and 17-dimethyluric acid) were measured by high performance liquid chromatography.
1. The influences of menstrual cycle on metabolic liver function
CYP1A2 activities were significantly different at the four stages of menstruation (p<0.05). The caffeine metabolic ratio was higher in Phase IV than in Phase I and II.Neither XO nor NAT activities changed during the four phases of menstrual cycle.
2. The change of the metabolic liver function in pregnancy
The activities of the three enzymes were changed significantly during the study periods (p<0.05). Both CYP1A2 and NAT activities were significantly lower in Phase I,II,and III than in Phase IV.In contrast, the XO activity was significantly decreasedin Phase I compared with phase III and IV.
As a conclusion, the menstrual cycle and pregnancy are conditions to be considered as influencing the liver metabolic function.