Pharmacokinetics of intravenous and oral pentoxifylline in healthy volunteers and in cirrhotic patients.
The pharmacokinetics of pentoxifylline were investigated in six healthy volunteers and in 10 patients with alcoholic cirrhosis. After a 100 mg intravenous infusion, pentoxifylline elimination half-life was prolonged in cirrhotic patients (2.12 +/- 1.22 hours versus 0.83 +/- 0.29 hours, p less than 0.05) because of a decrease in its plasma clearance (1.44 +/- 0.46 L.hr-1.kg-1 in patients with cirrhosis versus 3.62 +/- 0.75 L.hr-1.kg-1 in volunteers, p less than 0.001). The elimination half-life of the metabolite (5-hydroxypentoxifylline) was similar to that of the parent compound. After oral administration of a 400 mg sustained-released tablet, absolute bioavailability of pentoxifylline increased in cirrhotic patients (0.71 +/- 0.24 versus 0.33 +/- 0.13, p less than 0.01). Although plasma concentrations of pentoxifylline and hydroxypentoxifylline were significantly increased in cirrhotic patients, the AUCpentoxifylline/AUChydroxypentoxifylline ratio remained unchanged in both groups after either intravenous or oral administration. These findings show that liver cirrhosis profoundly alters the pharmacokinetics of pentoxifylline. However the formation of hydroxypentoxifylline is not modified in these patients, suggesting an extrahepatic metabolism.
Rames
A
A
Unité de Pharmacologie Clinique, Hôpital Saint-Antoine, Paris, France.
Poirier
J M
JM
LeCoz
F
F
Midavaine
M
M
Lecocq
B
B
Grange
J D
JD
Poupon
R
R
Cheymol
G
G
Jaillon
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013805:Theobromine / Q000031:analogs & derivatives*
D003692:Delayed-Action Preparations; D013607:Tablets; D013805:Theobromine; D010431:Pentoxifylline