Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog

  • 38 Accesses

  • 1 Citations

Summary

The study was aimed at investigating whether or not the kinetics of intravenously administered phenytoin (PT) was altered by oral administration of vigabatrin (VGB) or gabapentin (GBP).

A group of five beagle dogs were given a daily dose of PT (12 mg/kg, i.v.) for a period of 1 week. On day 8, plasma samples were serially collected over 24 hr. after administration of the PT dose. PT administration was continued with oral supplementary dose of VGB (60 mg/kg) for another week and then plasma samples were collected for analysis of PT levels. The same protocol was followed for the PT (12 mg/kg, IV) — GBP (300 mg caps., PO) study on a separate group (n=5) of dogs.

Orally administered GBP did not significantly alter the pharmacokinetic parameters of parentral PT. VGB, however markedly changed the drug’s kinetics as evidenced by a 31% (P=0.015) reduction in total body clearance (CL) and increase of over 45% in half-life (t1/2), (P=0.013) and area under the plasma PT concentration-time curve (AUC), (P=0.044).

GBP does not appear to have any pharmacokinetic interaction with PT, while coadministration of VGB and PT results in marked reduction in systemic clearance of the latter in the dog.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Sabers A., Gram L. (1992): Pharmacology of vigabatrin. Pharmacol. Toxicol., 70, 237–243.

  2. 2.

    Schechter P. (1989): Clinical pharmacology of vigabatrin. Br. J. Clin. Pharmacol., 27, 19S-22S.

  3. 3.

    Grant S., Heel R. (1991): Vigabatrin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs, 41, 889–926.

  4. 4.

    Elwes R., Binnie C. (1996): Clinical Pharmacokinetics of newer antiepileptic drugs: lamotrigine, vigabatrin, gabapentin and oxcarbazepine. Clin. Pharmacokinet, 30, 403–415.

  5. 5.

    Rimmer E., Kongola G., Richens A. (1988): Inhibition of the enzyme GABA — aminotrannsferase in human platelets by vigabatrin. Br. J. Clin. Pharmacol., 25, 251–259.

  6. 6.

    Andrews C., Fischer J. (1994): Gabapentin: a new agent for the management of epilepsy. Ann. Pharmacother, 28, 1188–1196.

  7. 7.

    Petroff O., Rothman D., Behar K. (1996): The effect of gabapentin of brain γ-aminobutyric acid in patients with epilepsy. Ann. Neurol., 39, 95–99.

  8. 8.

    Rimmer E., Richens A. (1989): Interaction between vigabatrin and phenytoin. Br. J. Clin. Pharmacol., 27, 27S-33S.

  9. 9.

    Browne T., Mattson R., Penry J., Smith D., Treiman D., Wilder B., Ben-Menachem E., Napoliello M., Sherry K., Szabo G. (1987): Vigabatrin for refractory complex partial seizures: multicentre single-blind study and long term follow-up. Neurol., 37, 187–189.

  10. 10.

    Tyndel F. (1994): Interaction of gabapentin with other antiepileptics (Letter). Lancet., 343, 1363–1364.

  11. 11.

    Anhut H., Leppik T., Schmidt B. (1988): Drug interaction study of the new anticonvulsant gabapentin with phenytoin in epileptic patients (abstract). Arch. Pharmacol., 337, R127.

  12. 12.

    Crawford P., Ghadiali E., Lane R., Blumhardt L., Chadwick D. (1987): Gabapenti as an antiepileptic drug in man. J. Neurol. Neurosurg. Psyychiatry, 50, 682–686.

  13. 13.

    Gibaldi M., Perrier D. (eds). (1982). Pharmacokinnetics. 2nd edition. New York: Marcel Dekker.

  14. 14.

    Riva R., Albani F., Contin M., Baruzzi A. (1996): Pharmacokinetic interaction between antiepileptic drugs: Clinical considerations. Clin. Pharmacokinet., 31, 470–493.

  15. 15.

    Anderson G. (1998): A mechanistic approach to antiepileptic drug interactions. Ann. Pharmacother., 32, 554–563.

  16. 16.

    Richens A. (1991): Pharmacology and clinical pharmacology of vigabatrin. J. Child. Neurol., 6, 2S7–2S10.

  17. 17.

    Hoensch H., Hutzel H., Kirch W., Ohnhaus E. (1985): Isolation of human hepatic microsomes and their inhibition by cimetidine and raintidine. Eur. J. Clin. Pharmacol. 29, 199–206.

Download references

Author information

Correspondence to K. M. Matar.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Matar, K.M., Nicholls, P.J., Tekle, A. et al. Effect of vigabatrin and gabapentin on phynytoin pharmacokinetics in the dog. Eur. J. Drug Metab. Pharacokinet. 25, 189–193 (2000). https://doi.org/10.1007/BF03192312

Download citation

Keywords

  • Phenytoin
  • Vigabatrin
  • Pharmacokinetic-interaction
  • Dogs