Drug treatment poses a therapeutic challenge in cystic fibrosis (CF) because the disposition of a number of drugs is altered in CF. Enhanced clearance of acetaminophen (APAP) and indocyanine green (ICG) have previously been reported in CF patients. The objective of the current study was to investigate if the CF-knockout mouse model (cftr m1UNC ) shows altered pharmacokinetics similar to those seen in CF patients using the 2 model compounds APAP and ICG. Clearance (CL/F) of APAP and renal (CL R ) and formation (CL f ) clearance of acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) were determined in CFknockout mice following administration of APAP (50 mg/kg, intraperitoneal). CL R of AS was 19.5 and 12.9 (mL/min per kg) and CL f of AS was 10.4 and 6.7 mL/min per kg for homozygous and heterozygous males, respectively, which was significantly different between groups. CL R of AG was 6.3 and 4.8 mL/min per kg and CL f of AG was 9.6 and 8.9 mL/min per kg for homozygous and heterozygous males, respectively, although not reaching statistical significance. No significant differences were noted in either Cl R or CL f of AG and AS in female CF mice. Plasma concentrations of ICG (10 mg/kg, intravenous) were determined over 0 to 15 minutes. Homozygous females showed a higher apparent volume of distribution (96 mL/kg) relative to heterozygous females (72 mL/kg). Similar to CF

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