Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs.
The disposition of pentoxifylline and two of its active metabolites (metabolite 1 [M1] and metabolite 5 [M5]) were studied following i.v. (8 mg/kg) and p.o. (30 mg/kg) administration to eight normal dogs using a randomized crossover design. Blood samples were collected at fixed time intervals after drug administration for determination of drug concentrations, platelet aggregation, and plasma fibrinogen. Complete blood counts, serum chemistry profiles, fibrinogen, and urinalysis were monitored at the beginning and end of each phase of the study (p.o. versus i.v. administration). Pentoxifylline was readily metabolized and bioavailable (50% +/- 26%). Both M1 and M5 were present throughout the study, with M5 predominating. Human drug therapeutic concentrations (1,000 ng/ml) were present for 170 +/- 24 minutes following i.v. administration and 510 +/- 85 minutes after p.o. dosing. These findings suggest that a 12-hour dosing regimen is appropriate. None of the dogs experienced any adverse effects after pentoxifylline administration. The lack of hematologic effects suggests that the immunologic effects of pentoxifylline may be of more importance in dogs.
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D006401:Hematologic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007275:Injections, Intravenous / Q000662:veterinary; D010431:Pentoxifylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*
D006401:Hematologic Agents; D010431:Pentoxifylline