The influence of liver dysfunction on the pharmacokinetics of carprofen

The pharmacokinetics of the investigational agent carprofen were examined in 12 patients with liver dysfunction (hepatic cirrhosis) and in six normal volunteers following single 100-mg oral administration of carprofen. In addition, three patients with acute hepatitis received a single 100-mg dose during the acute phase of the disease, and two of these patients received the same dose after they had convalesced. The pharmacokinetic parameters and urinary excretion data did not differ significantly (P greater than 0.05) between patients with hepatic cirrhosis and healthy volunteers. The mean +/- SD area under plasma concentration-time curve and apparent oral plasma clearance values were 57.8 +/- 11.7 micrograms X h/mL and 30.0 +/- 6.3 mL/min, respectively, in patients and 52.4 +/- 11.3 micrograms X h/mL and 33.1 +/- 7.2 mL/min in normals. The respective harmonic mean elimination half-lives were 10.5 and 9.4 hours. The 0-24 hour urinary recovery of intact drug and the glucuronide conjugate were 7.0 +/- 4.9% and 28.9 +/- 11.0%, respectively, in patients compared to 5.5 +/- 7.1% and 20.1 +/- 12.3% in normal subjects. The results of this study showed that liver dysfunction (hepatic cirrhosis) had no effect on the pharmacokinetic profile of carprofen. In the two patients with acute hepatitis who completed the study, the results suggest that the apparent oral clearance of carprofen may increase during the acute phase of the disease.