Rifampicin-induced elevation of serum bile acids in man

Abstract

Fasting and postprandial serum bile acid concentrations were determined by gas-liquid chromatography in 20 consecutive individuals (14 normal subjects, 6 cirrhotics) before and after administration of rifampicin in a single dose of 900 mg, using each individual as his own control. In the normal subjects the 2-hr postprandial level was 2.9 +/- 0.2 microM (mean +/- 1 SEM) prior to drug administration. Following rifampicin, it was 7.7 +/- 0.5 microM (P less than 0.0005). In the patients with liver cirrhosis the 2-hr postprandial level increased from 30.2 +/- 3.5 before, to 105.0 +/- 27.7 microM after rifampicin (P less than 0.025). Twelve hours after drug administration the levels of serum bile acids were not significantly different with respect to the control values. Total serum bilirubin also showed a transient and parallel increase. These findings are compatible with the hypothesis that rifampicin inhibits the hepatic transport of bile acids.

Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis

“…The second postulated mechanism of action of rifampicin is by inhibition of bile salt uptake by hepatocytes leading to a reduction in bile salt mediated disruption of hepatocyte membranes causing release of "pruritogens". 22 "Rifampicin hepatitis" was originally described by Scheuer et al in 1974 in a case series of 11 patients.…”

The pruritus of cholestasis

“…cholestasis), based on a reported experience in patients maintained on methadone treatment [96]. Interestingly, rifampicin is associated with an increase in serum bile acids concentrations [97]. Rifampicin can be hepatotoxic at doses used to manage pruritus [98]; thus, follow-up of liver tests is necessary if this drug is to be prescribed.…”

Human Organic Anion Transporting Polypeptide-C (SLC21A6) Is a Major Determinant of Rifampin-Mediated Pregnane X Receptor Activation

“…Indeed, impairment in the hepatic uptake of these organic anions by rifamycins is believed to be the mechanism involved in such drug-drug interactions Levi, 1973, 1974). Moreover, rifampin treatment is known to increase serum bile acid concentrations (Galeazzi et al, 1980;Berg et al, 1984), suggesting an interaction with hepatic bile acid transporters. Taken together, these findings indicate that the efficient hepatic clearance of rifamycins by human liver is facilitated by sinusoidal membrane uptake system(s) capable of endogenous and exogenous anion transport.…”