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Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral and intravenous administration of pentoxifylline to healthy adult horses

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  • 1 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 2 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 3 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
  • | 4 Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078.
  • | 5 Department of Chemistry, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL 32610.
  • | 6 Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

Abstract

Objective—To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses.

Animals—8 healthy adult horses.

Procedures—A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose.

Results—Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment.

Conclusions and Clinical Relevance—In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.

Abstract

Objective—To determine serum pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite in horses after administration of a single IV dose and after single and multiple oral doses.

Animals—8 healthy adult horses.

Procedures—A crossover study design was used with a washout period of 6 days between treatments. Treatments were IV administration of a single dose of pentoxifylline (8.5 mg/kg) and oral administration of generic sustained-release pentoxifylline (10 mg/kg, q 12 h, for 8 days). Blood samples were collected 0, 1, 3, 6, 12, 20, 30, and 45 minutes and 1, 2, 4, 6, 8, and 12 hours after IV administration. For oral administration, blood samples were collected 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, and 12 hours after the first dose and 0, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 hours after the last dose.

Results—Elimination of pentoxifylline was rapid after IV administration. After oral administration, pentoxifylline was rapidly absorbed and variably eliminated. Higher serum concentrations of pentoxifylline and apparent bioavailability were observed after oral administration of the first dose, compared with values after administration of the last dose on day 8 of treatment.

Conclusions and Clinical Relevance—In horses, oral administration of 10 mg of pentoxifylline/kg results in serum concentrations equivalent to those observed for therapeutic doses of pentoxifylline in humans. Twice daily administration appears to be appropriate. However, serum concentrations of pentoxifylline appear to decrease with repeated dosing; thus, practitioners may consider increasing the dosage if clinical response diminishes with repeated administration.

Contributor Notes

Dr. Cole's present address is Idexx Pharmaceuticals Inc, 4249 Piedmont Pkwy, Ste 105, Greensboro, NC, 27410.

Supported by the University of Florida, Veterinary Medical Center Resident Research Grant Competition and the American College of Veterinary Dermatology.

Presented in part at the North American Veterinary Dermatology Forum, Palm Springs, Calif, April 2006.

The authors thank Jennifer Lopez, Brett Rice, Ann Russell, Kirsten Wegner, and John Williams for technical assistance.

Address correspondence to Dr. Marsella.