European Journal of Clinical Pharmacology

, Volume 12, Issue 2, pp 133–136 | Cite as

The influence of allopurinol and size of dose on the metabolism of phenylbutazone in patients with gout

  • David Horwitz
  • Snorri S. Thorgeirsson
  • Jerry R. Mitchell
Originals

Summary

Administration of allopurinol 300 mg/day produced minimal changes in the disappearance of phenylbutazone in each of five subjects following single doses (6 mg/kg) in clinical range and caused some prolongation (21%, 52%) of drug half-lives in two of six subjects after single small doses (0.5 mg/kg); mean half-life was not significantly altered by allopurinol at either dose level (means of 52 versus 48 at 0.5 mg/kg and 68 versus 70 h at 6 mg/kg). Size of dose altered half-life when phenylbutazone was used alone; three subjects showed considerably longer half-lives at the higher dose (86 versus 47, 91 versus 41, 65 versus 38 h). Allopurinol caused a greater than 50% prolongation of half-lives in two of five subjects who received single 0.5 g doses of probenecid. These preliminary data do not indicate a need to change the dose of phenylbutazone when subjects are receiving allopurinol.

Key words

Phenylbutazone allopurinol probenecid metabolism gout 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Boston Collaborative Drug Surveillance Program: Allopurinol and cytotoxic drugs. Interaction in relation to bone marrow depression. J. Amer. Med. Ass.227, 1036–1040 (1974)Google Scholar
  2. 2.
    Brownlee, K. A.: Statistical Theory and Methodology in Science and Engineering, pp. 349–351. J. Wesley & Sons 1965Google Scholar
  3. 3.
    Burns, J. J., Rose, R. K., Chenkin, T., Goldman, A., Schulert, A., Brodie, B. B.: The physiological disposition of phenylbutazone (Butazolidin) in man and a method for its estimation in biological material. J. Pharmacol. Exp. Ther.109, 346–357 (1953)Google Scholar
  4. 4.
    Cho, A. K., Hodshon, B. J., Brodie, B. B.: Effects of phenylbutazone on liver microsomal demethylase. Biochem. Pharmacol.19, 1817–1823 (1970)Google Scholar
  5. 5.
    Comai, K., Gaylor, J. L.: Existence and separation of three forms of cytochrome P-450 from rat liver microsomes. J. Biol. Chem.248, 4947–4955 (1973)Google Scholar
  6. 6.
    Conney, A. H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev.19, 317–366 (1967)Google Scholar
  7. 7.
    Cunningham, J. L., Leyland, M. J., Delamore, I. W., Price Evans, D. A.: Acetanilide oxidation in phenylbutazone-associated hypoplastic anaemia. Brit. Med. J.1974 III, 313–317Google Scholar
  8. 8.
    Davies, D. S., Thorgeirsson, S. S.: Mechanism of hepatic drug oxidation and its relationship to individual differences in rates of oxidation in man. Ann. N.Y. Acad. Sci.179, 411–420 (1971)Google Scholar
  9. 9.
    Davies, D. S., Thorgeirsson, S. S., Breckenridge, A., Orme, M.: Interindividual differences in rates of drug oxidation in man. Drug Metab. Dipos.1, 411–417 (1973)Google Scholar
  10. 10.
    Dayton, P. G., Cucinell, S. A., Weiss, M., Perel, J. M.: Dosedependence of drug plasma level decline in dogs. J. Pharmacol. Exp. Ther.158, 305–316 (1967)Google Scholar
  11. 11.
    Dayton, P. G., Yü, T. F., Chen, W., Berger, L., West, L. A., Gutman, A. B.: The physiological disposition of probenecid, including renal clearance, in man, studied by an improved method for its estimation in biological material. J. Pharmacol. Exp. Ther.140, 278–286 (1963)Google Scholar
  12. 12.
    Elion, G. B., Callahan, S., Nathan, H., Bieber, S., Rundles, R. W., Hitchings, G. H.: Potentiation by inhibition of drug degradation: 6-substituted purines and xanthine oxidase. Biochem. Pharmacol.12, 85–93 (1963)Google Scholar
  13. 13.
    Kitagawa, H., Kamataki, T., Yoshida, S.: Studies on drug metabolism. IV. Effects of high dose administration of pentobarbital and phenylbutazone on the plasma biologic half lives in various species. Chem. Pharm. Bull.16, 2320–2323 (1968)Google Scholar
  14. 14.
    Mauer, E. F.: The toxic effects of phenylbutazone (Butazolidin). Review of the literature and report of the twenty-third death following its use. New Engl. J. Med.253, 404–409 (1955)Google Scholar
  15. 15.
    Nies, A. S., Oates, J. A.: Clinicopathologic conference: Hypertension and the lupus syndrome-revisited. Amer. J. Med.51, 812–814 (1971)Google Scholar
  16. 16.
    Tjandramaga, T. B., Cucinell, S. A., Israili, Z. H., Perel, J. M., Dayton, P. G., Yü, T. F., Gutman, A. B.: Observations on the disposition of probenecid in patients receiving allopurinol. Pharmacology8, 259–272 (1972)Google Scholar
  17. 17.
    Vesell, E. S., Page, J. G.: Genetic control of dicumarol levels in man. J. Clin. Invest.47, 2657–2663 (1968)Google Scholar
  18. 18.
    Vesell, E. S., Passananti, G. T., Greene, F. E.: Impairment of drug metabolism in man by allopurinol and nortriptyline. New Engl. J. Med.283, 1484–1488 (1970)Google Scholar
  19. 19.
    Weiner, M., Shapiro, S., Axelrod, J., Cooper, J. R., Brodie, B. B.: The physiological disposition of dicumarol in man. J. Pharmacol. Exp. Ther.99, 409–420 (1950)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • David Horwitz
    • 1
    • 2
  • Snorri S. Thorgeirsson
    • 1
    • 2
  • Jerry R. Mitchell
    • 1
    • 2
  1. 1.Hypertension-Endocrine Branch and the Laboratory of Chemical PharmacologyNational HeartLung
  2. 2.Blood Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations