TY - JOUR T1 - Acute phenobarbital administration alters the disposition of acetaminophen metabolites in the rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1129 LP - 1133 VL - 21 IS - 6 AU - K L Brouwer Y1 - 1993/11/01 UR - http://dmd.aspetjournals.org/content/21/6/1129.abstract N2 - The effects of acute phenobarbital (PB) administration on the disposition of acetaminophen (APAP), acetaminophen glucuronide (AG), and acetaminophen sulfate (AS) were examined in serum, bile, and urine of rats after a 100 mg/kg iv bolus dose of APAP. PB was administered intravenously as either an acute low (12 mg/kg) or high (60 mg/kg) dose to achieve PB serum concentrations equivalent to, or 5-fold higher than, PB concentrations in previous studies where impaired biliary excretion of AG and AS was noted after PB pretreatment for 5 days. Acute high-dose PB administration decreased the formation clearance of AG by 36% (from 3.14 +/- 0.64 to 2.00 +/- 0.70 ml/min/kg), resulting in a significant decrease in the percentage of the dose recovered in urine as AG. Decreased urinary recovery of AS after acute high-dose PB administration was due to an approximate 50% reduction in the renal clearance of AS (from 10.5 +/- 2.1 to 5.44 +/- 2.95 ml/min/kg). Although acute PB administration did not impair the biliary excretion of APAP or AS to a statistically significant extent, there was a trend toward decreased biliary excretion of AG. Large interanimal variability in AG biliary excretion was noted in rats receiving acute PB. These data indicate that serum PB concentrations are not related directly to impaired biliary excretion of AG or AS, and suggest that some other factor is responsible for the inhibition of AG and AS excretion at canalicular transport sites after PB pretreatment. ER -