Omapatrilat in patients with hepatic cirrhosis. Pharmacodynamics and pharmacokinetics.
OBJECTIVE
The pharmacodynamics and pharmacokinetics of omapatrilat, a member of a new class of cardiovascular compounds, the vasopeptidase inhibitors, were evaluated in subjects with hepatic cirrhosis (n = 10) and in healthy subjects (n = 10) matched for age, weight, gender and smoking history.


METHODS
All subjects received omapatrilat 25 mg orally once daily for 14 days. Plasma renin and urinary atrial natriuretic peptide (ANP) levels were measured to assess the effect of omapatrilat on cirrhotic subjects. The effect of omapatrilat on blood pressure as well as changes in ANP and plasma renin levels were not altered by hepatic impairment. Pharmacokinetic parameters were determined from plasma omapatrilat concentrations.


RESULTS
There were no significant differences between the two subject groups with regard to log-transformed area under the curve or maximum observed plasma concentration. Systemic accumulation was similar in the two groups.


CONCLUSIONS
These results suggest, based on findings in otherwise healthy cirrhotic subjects, that no adjustment of standard dosing regimens is indicated for hypertensive patients with mild to moderate cirrhosis.
O'Grady
P
P
Bristol-Myers Squibb PRI, Waterloo, Belgium.
Vesterqvist
O
O
Malhotra
B
B
Manning
J
J
Jemal
M
M
Ge
G
G
Mangold
B
B
D000284:Administration, Oral; D019540:Area Under Curve; D009320:Atrial Natriuretic Factor / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D012083:Renin / Q000097:blood; D013841:Thiazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D002317:Cardiovascular Agents; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D009320:Atrial Natriuretic Factor; D012083:Renin