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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1991 Apr;31(4):488–491. doi: 10.1111/j.1365-2125.1991.tb05568.x

Effect of zinc supplementation on oxidative drug metabolism in patients with hepatic cirrhosis.

M G Barry 1, P Macmathuna 1, K Younger 1, P W Keeling 1, J Feely 1
PMCID: PMC1368340  PMID: 2049261

Abstract

The pharmacokinetics of antipyrine were studied in seven zinc deficient patients with hepatic cirrhosis, before and after zinc supplementation. Each patient received zinc sulphate 660 mg daily for 30 days, restoring zinc status to normal as assessed by leucocyte zinc concentration. Antipyrine clearance was significantly reduced (P less than 0.05) and antipyrine elimination half-life increased (P less than 0.05) following administration of zinc sulphate without significant alteration in the apparent volume of distribution. It is concluded that supplementation of the zinc deficiency associated with hepatic cirrhosis impaired the hepatic oxidative metabolism of antipyrine.

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Selected References

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  1. BARTHOLOMAY A. F., ROBIN E. D., VALLEE R. L., WACKER W. E. Zinc metabolism in hepatic dysfunction. I. Serum zinc concentrations in Laënnec's cirrhosis and their validation by sequential analysis. N Engl J Med. 1956 Aug 30;255(9):403–408. doi: 10.1056/NEJM195608302550901. [DOI] [PubMed] [Google Scholar]
  2. Becking G. C., Morrison A. B. Hepatic drug metabolism in zinc-deficient rats. Biochem Pharmacol. 1970 Mar;19(3):895–902. doi: 10.1016/0006-2952(70)90252-2. [DOI] [PubMed] [Google Scholar]
  3. Bode J. C., Hanisch P., Henning H., Koenig W., Richter F. W., Bode C. Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology. 1988 Nov-Dec;8(6):1605–1609. doi: 10.1002/hep.1840080622. [DOI] [PubMed] [Google Scholar]
  4. Halsted J. A., Smith J. C., Jr Plasma-zinc in health and disease. Lancet. 1970 Feb 14;1(7642):322–324. doi: 10.1016/s0140-6736(70)90701-4. [DOI] [PubMed] [Google Scholar]
  5. Hartoma T. R., Sotaniemi E. A., Pelkonen O., Ahlqvist J. Serum zinc and serum copper and indices of drug metabolism in alcoholics. Eur J Clin Pharmacol. 1977 Oct 14;12(2):147–151. doi: 10.1007/BF00645136. [DOI] [PubMed] [Google Scholar]
  6. Hepner G. W., Vesell E. S. Aminopyrine disposition: studies on breath, saliva, and urine of normal subjects and patients with liver disease. Clin Pharmacol Ther. 1976 Dec;20(6):654–660. doi: 10.1002/cpt1976206654. [DOI] [PubMed] [Google Scholar]
  7. Keeling P. W., Jones R. B., Hilton P. J., Thompson R. P. Reduced leucocyte zinc in liver disease. Gut. 1980 Jul;21(7):561–564. doi: 10.1136/gut.21.7.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Keeling P. W., O'Day J., Ruse W., Thompson R. P. Zinc deficiency and photoreceptor dysfunction in chronic liver disease. Clin Sci (Lond) 1982 Jan;62(1):109–111. doi: 10.1042/cs0620109. [DOI] [PubMed] [Google Scholar]
  9. Parkki M. G. Inhibition of rat hepatic microsomal styrene oxide hydration by mercury and zinc in vitro. Xenobiotica. 1980 Apr;10(4):307–310. doi: 10.3109/00498258009033759. [DOI] [PubMed] [Google Scholar]
  10. Peters M. A., Fouts J. R. The influence of magnesium and some other divalent cations on hepatic microsomal drug metabolism in vitro. Biochem Pharmacol. 1970 Feb;19(2):533–544. doi: 10.1016/0006-2952(70)90210-8. [DOI] [PubMed] [Google Scholar]
  11. Prasad A. S. Clinical, endocrinological and biochemical effects of zinc deficiency. Clin Endocrinol Metab. 1985 Aug;14(3):567–589. doi: 10.1016/s0300-595x(85)80007-4. [DOI] [PubMed] [Google Scholar]
  12. Reding P., Duchateau J., Bataille C. Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet. 1984 Sep 1;2(8401):493–495. doi: 10.1016/s0140-6736(84)92567-4. [DOI] [PubMed] [Google Scholar]
  13. Shargel L., Cheung W. M., Yu A. B. High-pressure liquid chromatographic analysis of antipyrine in small plasma samples. J Pharm Sci. 1979 Aug;68(8):1052–1054. doi: 10.1002/jps.2600680835. [DOI] [PubMed] [Google Scholar]
  14. Sotaniemi E. A., Ahlqvist J., Pelkonen R. O., Pirttiaho H., Luoma P. V. Histological changes in the liver and indices of drug metabolism in alcoholics. Eur J Clin Pharmacol. 1977 Apr 20;11(4):295–303. doi: 10.1007/BF00607680. [DOI] [PubMed] [Google Scholar]
  15. Stevenson I. H. Factors influencing antipyrine elimination. Br J Clin Pharmacol. 1977 Jun;4(3):261–265. doi: 10.1111/j.1365-2125.1977.tb00710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Vesell E. S., Page J. G. Genetic control of drug levels in man: antipyrine. Science. 1968 Jul 5;161(3836):72–73. doi: 10.1126/science.161.3836.72. [DOI] [PubMed] [Google Scholar]
  17. Vesell E. S., Page J. G. Genetic control of the phenobarbital-induced shortening of plasma antipyrine half-lives in man. J Clin Invest. 1969 Dec;48(12):2202–2209. doi: 10.1172/JCI106186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Webb M., Cain K. Functions of metallothionein. Biochem Pharmacol. 1982 Jan 15;31(2):137–142. doi: 10.1016/0006-2952(82)90202-7. [DOI] [PubMed] [Google Scholar]
  19. Weismann K., Christensen E., Dreyer V. Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand. 1979;205(5):361–366. doi: 10.1111/j.0954-6820.1979.tb06065.x. [DOI] [PubMed] [Google Scholar]
  20. Whitehouse R. C., Prasad A. S., Rabbani P. I., Cossack Z. T. Zinc in plasma, neutrophils, lymphocytes, and erythrocytes as determined by flameless atomic absorption spectrophotometry. Clin Chem. 1982 Mar;28(3):475–480. [PubMed] [Google Scholar]
  21. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]
  22. Williams R. L., Mamelok R. D. Hepatic disease and drug pharmacokinetics. Clin Pharmacokinet. 1980 Nov-Dec;5(6):528–547. doi: 10.2165/00003088-198005060-00002. [DOI] [PubMed] [Google Scholar]

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