Pharmacokinetics of valsartan in patients with liver disease.
OBJECTIVE
Valsartan (CGP 48933), an orally active angiotensin II antagonist, is eliminated mainly by hepatic clearance. To characterize the compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsartan. In addition, to determine the exposure to valsartan when liver function is impaired, a pharmacokinetic study (open, single dose) was performed in patients with mild and moderate impairment of liver function.


METHODS
Biliary excretion of valsartan (after intravenous administration of 20 mg valsartan) was assessed in a patient who underwent a hepaticojejunostomy with subsequent bile drainage. Exposure to valsartan in patients with mild (n = 6) or moderate (n = 6) impaired liver function (Child's-Pugh classification) and matching (sex, age, and weight) healthy volunteers (n = 12) was studied after oral administration of a single dose of 160 mg valsartan.


RESULTS
After intravenous administration, valsartan was eliminated mainly as unchanged drug in the bile. Mean exposure (measured as area under the plasma valsartan concentration-time curve) to valsartan was increased about twofold in both the mild and the moderate groups compared with matched (age, sex, and weight) healthy volunteers.


CONCLUSIONS
These data are consistent with the pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.
Brookman
L J
LJ
Ciba Pharmaceuticals, Horsham, West Sussex, England.
Rolan
P E
PE
Benjamin
I S
IS
Palmer
K R
KR
Wyld
P J
PJ
Lloyd
P
P
Flesch
G
G
Waldmeier
F
F
Sioufi
A
A
Mullins
F
F
D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D004322:Drainage; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008107:Liver Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine