Dose-response effects of pentoxifylline on erythrocyte filterability: clinical and animal model studies.
Ten patients with chronic occlusive arteriosclerosis received single oral doses of 100, 200, 400, 800, and 1200 mg pentoxifylline in a single-blind, placebo-controlled study. Blood samples were drawn at baseline and at 2 hour intervals for 6 hours. Drug and metabolite levels, as well as red cell filterability (deformability), were determined on all blood samples. Statistically significant dose-response increases of red cell filterability were found 4 and 6 hours after oral medication with the dosages of 200 to 1200 mg pentoxifylline. These changes were proportional to the plasma levels of pentoxifylline and metabolites 1 and 5 of this agent. Attempts were made to develop a suitable animal-screening method for agents with similar activity and to determine whether red blood cells in the absence of disease-related abnormalities may respond to this type of therapy. Five healthy Macaca arctoides monkeys were given 24 mg/kg pentoxifylline intravenously, and measurable but lesser increases in red cell deformability were recorded than in the patients.
Roswell Park Memorial Institute, State University of New York, Buffalo 14263.
J L
JL
Ambrus
J M
JM
Anain
S M
SM
Anain
P M
PM
Anain
J M
JM
Anain
S
S
Stadler
P
P
Mitchell
J A
JA
Brobst
B L
BL
Cobert
J P
JP
Savitsky
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004907:Erythrocyte Deformability / Q000187:drug effects*; D005260:Female; D006801:Humans; D008251:Macaca; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D016037:Single-Blind Method; D013805:Theobromine / Q000031:analogs & derivatives*
D013805:Theobromine; D010431:Pentoxifylline