Pharmacokinetics of flosequinan in patients with heart failure.
OBJECTIVE
The pharmacokinetics of flosequinan were studied in a group of 18 patients with chronic cardiac failure.


RESULTS
After a single dose of 100 mg, Cmax of the parent compound (2.52 mg.l-1) was recorded at 1.4 h, and of the sulphone metabolite flosequinoxan at 21.7 h. The plasma elimination half lives of the parent compound (6.4 h) and of the metabolite (54.3 h) were prolonged compared to previous studies in normal volunteers. After repeated dose administration for 36 days, the kinetics of the parent compound and metabolite remained essentially unchanged with an expected significant accumulation of metabolite (Cmax 8.4 vs 3.21 mg.l-1). No adverse effects were observed.


CONCLUSIONS
It is possible that altered drug kinetics in patients with heart failure, probably related to altered hepatic blood flow, could contribute to drug toxicity.
Nicholls
D P
DP
Royal Victoria Hospital, Belfast, Northern Ireland.
Droogan
A
A
Carson
C A
CA
Taylor
I C
IC
Passmore
A P
AP
Johnston
G D
GD
Kendall
M
M
Dutka
D
D
Morris
G K
GK
Underwood
L M
LM
Hind
I D
ID
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics*
D011804:Quinolines; D014665:Vasodilator Agents; C047316:flosequinan