PHARMACOKINETICS OF VALSARTAN IN PATIENTS WITH LIVER-DISEASE

Objectives: Valsartan (CGP 48933), an orally active angiotensin II ant agonist, is eliminated mainly by hepatic clearance. To characterize th e compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsa rtan, In addition, to determine the exposure to valsartan when liver f unction is impaired, a pharmacokinetic study (open, single dose) was p erformed in patients with mild and moderate impairment of liver functi on. Patients: Biliary excretion of valsartan (after intravenous admini stration of 20 mg valsartan) was assessed in a patient who underwent a hepaticojejunostomy with subsequent bile drainage. Exposure to valsar tan in patients with mild (n = 6) or moderate (n = 6) impaired liver f unction (Child's-Pugh classification) and matching (sex, age, and weig ht) healthy volunteers (n = 12) was studied after oral administration of a single dose of 160 mg valsartan. Results: After intravenous admin istration, valsartan was eliminated mainly as unchanged drug in the bi le. Mean exposure (measured as area under the plasma valsartan concent ration-time curve) to valsartan was increased about twofold in both th e mild and the moderate groups compared with matched (age, sex, and we ight) healthy volunteers. Conclusion: These data are consistent with t he pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.