The cause of
pruritus of
cholestasis is unknown. We have hypothesized that
pruritus may be caused by an indirect effect of high hepatic concentrations of toxic
bile acids. To test this hypothesis, we have conducted a double-blind, controlled, crossover clinical trial of
rifampin, an agent that inhibits hepatic
bile acid uptake and may detoxify hepatic
bile acids by stimulation of
mixed-function oxidases. Nine patients with
primary biliary cirrhosis received 300-450 mg/day of
rifampin and placebo sequentially, in random order. Each treatment was administered for 14 days, with a 14-day washout between treatments. Endpoints included patient preference, changes in a daily visual analogue scale
pruritus score, and amount of
cholestyramine ingested.
Antipyrine elimination rates and serum
bile acids were tested at the end of each treatment period. All 9 patients completed the trial and 8 of them preferred
rifampin to placebo (p = 0.03). There were no adverse reactions. Visual analogue scale
pruritus scores showed no significant placebo response or any effect from the order of treatment, but did show a highly significant reduction in
pruritus in response to
rifampin (p less than 0.002). This effect was evident within the first week of
rifampin treatment.
Rifampin produced a 33% reduction in
antipyrine plasma half-life, but no change in fasting total serum
bile acids.
Cholestyramine usage did not change significantly. We conclude that
rifampin is useful for short-term relief of
pruritus in
primary biliary cirrhosis; however, the mechanism of this effect is unknown. Longer trials are needed, as are trials in other cholestatic disorders.