Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle
This study investigated the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after single-dose intravenous (IV) administration (10 mg/kg) of PTX in six healthy cattle. The safety of PTX was evaluated by clinical observation and biochemical analysis. Plasma concentrations of PTX and M-I were simultaneously determined by reverse-phase high performance liquid chromatography. Pharmacokinetic parameters were calculated using non-compartmental methods. Salivation and discomfort were observed for 2 h following the drug administration. Serum direct bilirubin, total bilirubin, and phosphorus levels at 24 h following the drug administration were significantly different from the control values (0 h) (P < 0.05). Pharmacokinetic variables of PTX were characterized by a short terminal elimination half-life (1.05 ± 0.19 h), a large volume of distribution (6.30 ± 1.76 L/kg), and high total body clearance (5.31 ± 1.27 L/h/kg). The mean ratio between the area under the concentration-time curves of M-I and PTX was 1.34. These results indicate that single-dose administration of PTX at 10 mg/kg IV in cattle resulted in therapeutic concentrations similar to those observed in humans and horse. However, further studies are necessary to determine the safety and pharmacokinetics following repeated administrations of PTX.
KeywordsPentoxifylline M-I metabolite Pharmacokinetics Intravenous Cattle
This study was presented in abstract form as a poster presentation in the 3rd International Convention of Pharmaceuticals and Pharmacies, Istanbul, Turkey, 26–29 April 2017.
Compliance with ethical standards
The animal experiment was conducted in accordance with the procedure of Committee on Animal Use Ethics (Approval No. 2015/96).
Conflict of interest
The authors declare that they have no conflict of interest.
- Italiya, K.S., Sharma, S., Kothari, I., Chitkara, D., and Mittal, A., 2017. Simultaneous estimation of lisofylline and pentoxifylline in rat plasma by high performance liquid chromatography-photodiode array detector and its application to pharmacokinetics in rat, Journal of Chromatography B, 1061, 49–56.CrossRefGoogle Scholar
- Liska, D.A., Akucewich, L.H., Marsella, R., Maxwell, L.K., Barbara, J.E., and Cole, C.A., 2006. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after oral and intravenous administration of pentoxifylline to healthy adult horses, American Journal of Veterinary Research, 67, 1621–1627.CrossRefGoogle Scholar
- Radostitis, O.M., Gay, C.C., Blood, D.C., and Hinchcliff, K.W., 2007. Veterinary Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. 10th ed, (W. B. Saunders, London), 2048–2050.Google Scholar
- Rames, A., Poirier, J.M., LeCoz, F., Midavaine, M., Lecocq, B., Grange, J.D., Poupon, R., Cheymol, G., and Jaillon, P., 1990. Pharmacokinetics of intravenous and oral pentoxifylline in healthy volunteers and in cirrhotic patients, Clinical Pharmacology & Therapeutics, 47, 354–359.CrossRefGoogle Scholar
- Rees, C., Boothe, D.M., Boeckh, A., Wilkie, S., Esparza, T., and Green, R., 2003. Dosing regimen and hematologic effects of pentoxifylline and its active metabolites in normal dogs, Veterinary Therapeutics: Research in Applied Veterinary Medicine, 4, 188–196.Google Scholar
- Sykes, J.E., and Papich, M.P., 2014. Antiviral and Immunomodulatory Drugs, In: Sykes, J.E. (ed), Canine and Feline Infectious Diseases (Elsevier Saunders, St. Louis, Missouri 63043), 54–65.Google Scholar
- Szotáková, B., Baliharová, V., Lamka, J., Nožinová, E., Wsól, V., Velık, J., Machala, M., Neča, J., Souček, P., Šusová, S., and Skálová, L., 2004. Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep, Research in Veterinary Science, 76, 43–51.CrossRefGoogle Scholar