Reduction of hyperbilirubinemia with hypericum extract (St. John's Wort) in a patient with Crigler-Najjar syndrome type II

Br J Clin Pharmacol. 2016 May;81(5):1002-4. doi: 10.1111/bcp.12869. Epub 2016 Mar 7.

Abstract

Aims: Crigler-Najjar syndrome (CN) type II is a congenital disease with unconjugated hyperbilirubinemia due to a deficiency of uridine 5'-diphospho-glucuronosyltransferase 1A1. Since the currently proposed treatment with phenobarbital is associated with adverse reactions, we investigated the effect of hypericum extract.

Methods: Repetitive determination of total serum bilirubin in a female with CN type II before, during and after daily treatment with 900 mg hypericum extract on two occasions for 8 weeks. Confirmation of the enzyme-inducing effect of hypericum using the cytochrome P450 3A4 probe drug i.v. midazolam.

Results: Hypericum reduced midazolam exposure by 42% and the total serum bilirubin concentration by 30 to 35%.

Conclusions: Hypericum extract is a potential alternative to phenobarbital in patients with CN type II.

Keywords: Crigler-Najjar syndrome; hyperbilirubinemia; hypericum; uridine 5′-diphospho-glucuronosyltransferase 1A1.

Publication types

  • Case Reports
  • Letter

MeSH terms

  • Adult
  • Area Under Curve
  • Bilirubin / blood
  • Crigler-Najjar Syndrome / drug therapy*
  • Crigler-Najjar Syndrome / genetics
  • Cytochrome P-450 CYP3A / biosynthesis
  • Cytochrome P-450 CYP3A / metabolism*
  • Enzyme Induction / drug effects
  • Female
  • GABA Modulators / pharmacokinetics
  • GABA Modulators / therapeutic use
  • Glucuronosyltransferase / genetics
  • Humans
  • Hyperbilirubinemia / drug therapy*
  • Hypericum
  • Midazolam / administration & dosage
  • Midazolam / pharmacokinetics
  • Phenobarbital / therapeutic use
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*
  • Pregnane X Receptor
  • Receptors, Steroid / metabolism
  • Young Adult

Substances

  • GABA Modulators
  • Hypericum extract LI 160
  • Plant Extracts
  • Pregnane X Receptor
  • Receptors, Steroid
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Midazolam
  • Bilirubin
  • Phenobarbital

Supplementary concepts

  • Crigler Najjar syndrome, type 2