Effects of phenobarbital on bilirubin metabolism and its response to phototherapy in the jaundiced gunn rat

Authors

  • Arnold N. Cohen,

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Current affiliation:
    1. Suite 234 St. Luke's Medical Building, 714 South Cowley Street, Spokane, Washington 99202
    Search for more papers by this author
  • Jaime Kapitulnik,

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Search for more papers by this author
  • J. Donald Ostrow M.D.,

    Corresponding author
    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    • Veterans Administration Lakeside Medical Center (111-G), 333 East Huron Street, Chicago, Illinois 60611
    Search for more papers by this author
  • Eugene A. Zenone,

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Current affiliation:
    1. Gastroenterology Section, Crozier-Chester Medical Center, 15th and Upland Avenue, Chester, Pennsylvania 19013
    Search for more papers by this author
  • Cecile Cochrane,

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Search for more papers by this author
  • Lillian Celic,

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Search for more papers by this author
  • Heidemarie Cheney

    1. Gastroenterology Section, Department of Medicine, Veterans Administration Lakeside Medical Center and Northwestern University, Chicago, Illinois, 60611
    2. The Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
    3. The Veterans Administration Medical Center, Philadelphia, Pennsylvania 19104
    Search for more papers by this author

Abstract

Jaundiced Gunn rats, treated with phenobarbital (60 mg per kg i.p. for 7 to 10 days) showed 25 and 36% decreases in mean plasma bilirubin levels in two experiments (p < 0.01). Kinetic studies with tracer 14C-bilirubin revealed that there was no change in bilirubin turnover or total pool size due to phenobarbital, but a 49% increase in the hepatic pool and a 27% decrease in the cutaneous pool of bilirubin. The increase in the hepatic pool accounted for over 90% of the bilirubin lost from the plasma. Such pretreatment with phenobarbital did not alter the decline in plasma bilirubin or total bilirubin pool due to subsequent phototherapy. Phenobarbital followed by phototherapy produced a significantly greater reduction in plasma bilirubin levels than either treatment alone. These studies demonstrate that phenobarbital does decrease plasma bilirubin in Gunn rats primarily by shifting the pigment to the liver, and suggests that combined treatment with phenobarbital and phototherapy might be of value in patients with congenital hyperbilirubinemia due to glucuronyl transferase deficiency.

Ancillary