Pharmacokinetics of indoramin and its metabolite 6-hydroxyindoramin after single and multiple doses to cirrhotic liver patients.
Pharmacokinetic data obtained after intravenous and single and repeat chronic oral dosing of indoramin in nine patients with liver cirrhosis are described. Median plasma clearance is 11.2 ml/min/kg. Terminal disposition half-life is prolonged after intravenous as well as acute and chronic oral dosing (9.1 versus 10.7 versus 12.2 h). Median volume of distribution is 11.2 L/kg. Bioavailability is increased with a wide range of distribution from 12.2 to 75.4%. There is a slight tendency of accumulation during twice daily oral dosing that cannot be explained by the degree of prolongation of half-life. The kinetics of the main metabolite, 6-hydroxyindoramin, are substantially comparable to the kinetics of indoramin with a ratio of 6-hydroxyindoramin/indoramin calculated from the area under plasma concentration-time curve of 0.3, which is within the range of normal. All data suggest that the changed pharmacokinetics are due to altered liver perfusion as would be expected from a substance with a plasma clearance in the magnitude of liver perfusion in normal volunteers. It seems likely that, in patients with liver cirrhosis, similar alpha 1 blocking effects may be achieved with lower doses than in patients with normal liver function.
G
G
Neumann
G
G
Wilke
W V
WV
Reimold
D M
DM
Pierce
M
M
Giesing
D000284:Administration, Oral; D001711:Biotransformation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood*; D007217:Indoramin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D007275:Injections, Intravenous; D007700:Kinetics; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged
D007211:Indoles; D007217:Indoramin; C049268:6-hydroxyindoramin