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

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.

Figure 1

Effect of hypericum extract on midazolam exposure and serum bilirubin concentrations in a patient with Crigler‐Najjar syndrome type II. The patient was treated with 900 mg hypericum extract per day for 8 weeks on 2 occasions 18 months apart (Figure 1C,D). Before and during the first treatment period, CYP3A4 activity was assessed by i.v. midazolam (Figure 1A,B). The dotted lines in Figure 1C,D indicate two standard deviations (SD) of the averaged serum bilirubin concentrations before treatment. See text for further explanations.