Effect of rifampicin treatment on hepatic drug metabolism and serum bile acids in patients with primary biliary cirrhosis

Abstract

Six patients with primary biliary cirrhosis (PBC) were treated with a daily oral dose of 600 mg rifampicin for 2 weeks to induce the hepatic metabolism of drugs and bile acids. On rifampicin 5 of 6 patients experienced a pronounced decrease of their pruritus. In all patients the oxidative cytochrome P-450 dependent drug metabolism was induced as shown by an increase of antipyrine-clearance from 36.3 +/- 8.8 to 80.6 +/- 20.1 ml/min and an enhanced urinary excretion of 6-beta-hydroxycortisol from 454 +/- 1.99 to 1607 +/- 362 micrograms/24 h. Furthermore, in all 6 patients the serum alkaline phosphatase declined. In the 3 cholestatic patients (bilirubin greater than 1.0 mg/dl) the serum concentration of total and conjugated bile acids was strikingly reduced. Thus, rifampicin is an inducer of hepatic metabolism in PBC-patients, ameliorates the pruritus and can lower serum concentrations of alkaline phosphatase and bile acids.

Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients.

“…Although this commonly used antibiotic does not at all induce P-450p in the rat (23) it is an effective inducer of the orthologous liver enzyme, LM3c (23), in the rabbit. Treatment of patients with rifampicin increases production of 6 f-hydroxysteroids in the urine (38). Because HLp appears to be the major steroid 6 ,B-hydroxylase in human liver (39) induction of HLp by rifampicin would provide an explanation for these earlier observations and the breath test results presented here.…”

Induction and autoinduction properties of rifamycin derivatives: a review of animal and human studies.

“…Bilirubin undergoes glucuronidation prior to excretion in the bile. There are data suggesting that RIM might enhance the hepatic clearance of bilirubin (36)(37)(38). However, in a study conducted in subjects given RIM for 30 days, bilirubin GT activity was reported to be insensitive to the treatment (39).…”

Successful treatment of severe unconjugated hyperbilirubinemia via induction of UGT1A1 by rifampicin

“…Significant decreases of transaminases [10,12], gamma-glutamyltransferase [10,12,13], alkaline phosphatase [10] and total bile salt levels [8,10,12] were observed. Bilirubin was not significantly affected in the study populations mentioned [7][8][9][10][11][12][13], but there was a trend towards lower levels in one long-term study [12]. However, at least two patients from other studies are likely to have shown clear reductions of bilirubin during treatment with rifampicin: There was a decline observed from 9.0 to 2.9 mg/dl in [7], and from 16.80 to 10.50 mg/dl in [8].…”

“…Before the common use of UDCA in cholestatic liver disease was established [6], small trials with rifampicin in cholestatic liver disease had shown marked improvement of pruritus [7][8][9][10][11][12][13]. In PBC, three trials administered rifampicin for 2 weeks [8][9][10].…”

“…In PBC, three trials administered rifampicin for 2 weeks [8][9][10]. Two studies followed patients for 8 and 2-24 months, respectively, on open-label rifampicin [11,12].…”