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

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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.

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  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)

  2. 2.

    Brownlee, K. A.: Statistical Theory and Methodology in Science and Engineering, pp. 349–351. J. Wesley & Sons 1965

  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)

  4. 4.

    Cho, A. K., Hodshon, B. J., Brodie, B. B.: Effects of phenylbutazone on liver microsomal demethylase. Biochem. Pharmacol.19, 1817–1823 (1970)

  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)

  6. 6.

    Conney, A. H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev.19, 317–366 (1967)

  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, 313–317

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  15. 15.

    Nies, A. S., Oates, J. A.: Clinicopathologic conference: Hypertension and the lupus syndrome-revisited. Amer. J. Med.51, 812–814 (1971)

  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)

  17. 17.

    Vesell, E. S., Page, J. G.: Genetic control of dicumarol levels in man. J. Clin. Invest.47, 2657–2663 (1968)

  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)

  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)

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Horwitz, D., Thorgeirsson, S.S. & Mitchell, J.R. The influence of allopurinol and size of dose on the metabolism of phenylbutazone in patients with gout. Eur J Clin Pharmacol 12, 133–136 (1977).

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Key words

  • Phenylbutazone
  • allopurinol
  • probenecid
  • metabolism
  • gout