Effect of nonuniform bile flow rate on the rate of biliary excretion of bromophenol blue in the beagle.

Following the intravenous administration of bromophenol blue to beagle dogs, graphs of the biliary excretion rate versus time displayed drastic fluctuations which render them of little value for standard pharmacokinetic modeling purposes. It was shown that these fluctuations in excretion rate are highly correlated with corresponding fluctuations in the bile flow rate. An expression was derived which accounts for the primary effect of nonuniform bile flow rate on the biliary excretion rate. This treatment would enable the use of such biliary excretion rate data for pharmacokinetic modeling. Secondary effects of nonuniform bile flow on the biliary excretion rate are also discussed. It is suggested that the modeling of other flow rate-dependent elimination processes could benefit from such a treatment.