Liver blood flow and enzyme induction in man

Area of Science:

• Pharmacology
• Hepatology
• Physiology

Background:

• Liver microsomal enzyme induction is known to increase liver blood flow in animal models.
• Previous studies in rats and monkeys suggested a link between enzyme induction and enhanced hepatic blood flow.

Purpose of the Study:

• To investigate the effect of liver microsomal enzyme induction on liver blood flow and metabolic markers in human volunteers.
• To quantify changes in antipyrine clearance, liver volume, and specific biochemical markers following enzyme induction.

Main Methods:

• Seven human volunteers underwent measurements of liver blood flow (133Xenon inhalation), liver volume (99mTechnetium-sulfur-colloid scan), and biochemical markers (antipyrine, gamma GT, d-glucaric acid, 6-beta-hydroxycortisol).
• Measurements were repeated after 14 days of daily 1,000 mg antipyrine administration to induce liver microsomal enzymes.

Main Results:

• Antipyrine administration significantly decreased antipyrine half-life and increased antipyrine clearance.
• Urinary excretion of d-glucaric acid and 6-beta-hydroxycortisol, and serum gamma-GT levels were significantly elevated.
• Liver blood flow per unit mass increased significantly (p < 0.02), and total liver blood flow increased significantly (p < 0.02) from 590 ml/min to 809 ml/min.

Conclusions:

• Enzyme induction with antipyrine significantly enhances total liver blood flow in humans.
• The study confirms that liver microsomal enzyme induction leads to increased hepatic blood flow, supporting findings in animal models.