Disposition of drugs in cystic fibrosis. II. Hepatic blood flow.
To determine whether the increased clearance of high extraction-ratio drugs in cystic fibrosis is caused by an increase in hepatic blood flow, the blood flow in main branches of the hepatic vein and portal vein was measured by use of noninvasive duplex ultrasound scanning in 10 adult subjects with cystic fibrosis and in 10 healthy age-, gender-, and height-matched control subjects. No statistically significant differences between subjects with cystic fibrosis and control subjects were detected in either the hepatic vein (217 +/- 103 ml/min for subjects with cystic fibrosis versus 211 +/- 135 ml/min for control subjects) or the portal vein (205 +/- 114 ml/min for subjects with cystic fibrosis versus 190 +/- 101 ml/min for control subjects) blood flows. These data indicate that a large (greater than or equal to 100%) increase in the clearance of high extraction-ratio drugs in patients with cystic fibrosis is unlikely to be primarily caused by an increase in hepatic blood flow. It is probable that alternative mechanisms such as enhanced secretory or metabolic pathways account in large part for increases in clearance of high extraction-ratio drugs.
O'Sullivan
T A
TA
Department of Pharmacy Practice, University of Washington, Seattle 98195.
Bauer
L A
LA
Horn
J R
JR
Zierler
B K
BK
Strandness
D E
DE
Williams-Warren
J
J
Smith
A L
AL
Unadkat
J D
JD
D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006503:Hepatic Veins / Q000000981:diagnostic imaging; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008102:Liver Circulation; D008297:Male; D011169:Portal Vein / Q000000981:diagnostic imaging; D014463:Ultrasonography
D007208:Indocyanine Green