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Animal models prepared by treatment with carbon tetrachloride (CCl(4)) have been used to examine drug disposition in hepatic disorder. However, previous studies demonstrated that systemic administration of CCl(4) impaired not only hepatic but also renal function. We recently reported that application of CCl(4) to the rat liver surface produced hepatic damage without impairing renal function. In the present study, we examined the pharmacokinetics of phenol red in our developed rat model. The rats treated with CCl(4) by liver surface application exhibited decreases in the biliary clearance of phenol red in comparison with normal rats from 0.54+/-0.03 to 0.31+/-0.06 ml/min, suggesting hepatic damage. In these rats, the renal clearance of phenol red did not decrease (0.50+/-0.16 ml/min vs. 0.46+/-0.07 ml/min in normal rats). On the other hand, oral and intraperitoneal treatments with CCl(4) reduced not only the biliary clearance of phenol red (0.34+/-0.03 ml/min in p.o. treated rats, 0.18+/-0.01 ml/min in i.p. treated rats) but also the renal clearance (0.26+/-0.05 ml/min in p.o. treated rats, 0.18+/-0.06 ml/min in i.p. treated rats) as compared with normal rats. These findings indicate that the rat model of liver damage prepared by liver surface application of CCl(4) is useful to investigate the effects of hepatic disorder on the pharmacokinetics of drugs.

Pharmacokinetics of Phenol Red in Rat Models of Liver Damage Prepared by Liver Targeting of Carbon Tetrachloride