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Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle

  • Kamil Uney
  • Bunyamin Tras
  • Orhan Corum
  • Ramazan Yildiz
  • Mehmet Maden
Regular Articles

Abstract

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.

Keywords

Pentoxifylline M-I metabolite Pharmacokinetics Intravenous Cattle 

Notes

Acknowledgements

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.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Kamil Uney
    • 1
  • Bunyamin Tras
    • 1
  • Orhan Corum
    • 2
  • Ramazan Yildiz
    • 3
  • Mehmet Maden
    • 4
  1. 1.Department of Pharmacology and Toxicology, Faculty of Veterinary MedicineUniversity of SelcukKonyaTurkey
  2. 2.Department of Pharmacology and Toxicology, Faculty of Veterinary MedicineUniversity of KastamonuKastamonuTurkey
  3. 3.Department of Internal Medicine, Faculty of Veterinary MedicineUniversity of Mehmet Akif ErsoyBurdurTurkey
  4. 4.Department of Internal Medicine, Faculty of Veterinary MedicineUniversity of SelcukKonyaTurkey

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