Pharmacokinetics of pentoxifylline in dogs after oral and intravenous administration.
OBJECTIVE
To evaluate the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl-metabolite, metabolite 1 (M1), in dogs after IV administration of a single dose and oral administration of multiple doses.


METHODS
7 sexually intact, female, mixed-breed dogs.


METHODS
A crossover study design was used so that each of the dogs received all treatments in random order. A drug-free period of 5 days was allowed between treatments. Treatments included IV administration of a single dose of PTX (15 mg/kg of body weight), oral administration of PTX with food at a dosage of 15 mg/kg (q 8 h) for 5 days, and oral administration of PTX without food at a dosage of 15 mg/kg (q 8 h) for 5 days. Blood samples were taken at 0.25, 0.5, 1, 1.5, 2, 2.5, and 3 hours after the first and last dose of PTX was administered PO, and at 5, 10, 20, 40, 80, and 160 minutes after PTX was administered IV.


RESULTS
PTX was rapidly absorbed and eliminated after oral administration. Mean bioavailability after oral administration ranged from 15 to 32% among treatment groups and was not affected by the presence of food. Higher plasma PTX concentrations and apparent bioavailability were observed after oral administration of the first dose, compared with the last dose during the 5-day treatment regimens.


CONCLUSIONS
In dogs, oral administration of 15 mg of PTX/kg results in plasma concentrations similar to those produced by therapeutic doses in humans, and a three-times-a-day dosing regimen is the most appropriate.
Marsella
R
R
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610, USA.
Nicklin
C F
CF
Munson
J W
JW
Roberts
S M
SM
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D002853:Chromatography, Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000662:veterinary; D006207:Half-Life; D006401:Hematologic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous / Q000662:veterinary; D010431:Pentoxifylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011897:Random Allocation
D006401:Hematologic Agents; D010431:Pentoxifylline