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D-Penicillamine

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Critical Care Toxicology

Abstract

D-penicillamine (DPA) is a heavy metal chelator and is the drug of choice for management of Wilson’s disease, a copper-overload disease state. It may also be effective in arsenic, mercury, and lead chelation. Although the toxicity of DPA is relatively low, there are more effective and less toxic chelators, for most heavy metals, with the exception of copper. This chapter focuses on the general uses of D-penicillamine as a chelator. L-penicillamine is not used clinically due to its strong inhibition of pyridoxine-dependent enzymes, leading to neurotoxicity in animal experiments.

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References

  1. Abraham EP, et al. Penicillamine, a characteristic degradation product of penicillin. Nature. 1943;151:107–7. 23 January 1943.

    Google Scholar 

  2. Walshe JM. Historical review: the story of penicillamine: a difficult birth. Mov Disord. 2003;18(8):853.

    Article  PubMed  Google Scholar 

  3. Boulding JE, Baker RA. Lancet. 1957;2:985.

    Article  Google Scholar 

  4. Goldberg A, et al. Treatment of lead-poisoning with oral penicillamine. Br Med J. 1963;1:1270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ohlsson WTL. Penicillamine as lead-chelating substance in man. Br Med J. 1962;1:1454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Perrett D. An outline of D-penicillamine metabolism. J R Soc Med. 1977;70 Supplement 3:61–4.

    Google Scholar 

  7. Joyce DA, Day RO, Murphy BR. The pharmacokinetics of albumin conjugates of D-penicillamine in humans. Drug Metab Dispos. 1991;19(2):309–11.

    CAS  PubMed  Google Scholar 

  8. Schuna A, Osman MA, Patel RB, Welling PG, Sundstrom WR. Influence of food on the bioavailability of penicillamine. J Rheumatol. 1983;10(1):95–7.

    CAS  PubMed  Google Scholar 

  9. Osman MA, et al. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther. 1983;33(4):465–70.

    Article  CAS  PubMed  Google Scholar 

  10. Swaran JD, Flora, Vidhu. Chelation in metal intoxication. Int J Environ Res Public Health. 2010;7:2745–88.

    Article  Google Scholar 

  11. Joyce DA, Day RO. D-penicillamine and D-penicillamine-protein disulphide in plasma and synovial fluid of patients with rheumatoid arthritis. Br J Clin Pharmacol. 1990;30:511–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anderson O. Principles and recent developments in chelation treatment of metal intoxication. Chem Rev. 1999;99(9):2683–710.

    Article  Google Scholar 

  13. Muijsers AO, van de Stadt RJ, Henrichs AMA. D-penicillamine in patients with rheumatoid arthritis: serum levels, pharmacokinetic aspects, and correlation with clinical course and side effects. Arthitis Rheum 1984;27:1362–69. Perrett D. An outline of D-penicillamine metabolism. Proc R Soc Med. 1977;70(supp 3): 61–4.

    Google Scholar 

  14. Netter P, Bannwarth B, Pere P, Nicolas A. Clinical pharmacokinetics of D-penicillamine. Clin Pharmacokinet. 1987;13(5):317–33.

    Article  CAS  PubMed  Google Scholar 

  15. Wei P, Sass-Kortsak A. Urinary excretion and renal clearances of D-penicillamine in humans and the dog. Gastroenterology. 1970;58:288.

    Google Scholar 

  16. Blanusa M, Varnai VM, et al. Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12:2771–94.

    Article  CAS  PubMed  Google Scholar 

  17. Sarkar B, Sass-Korsak K et al. A comparative study of in vitro and in vivo interaction of D-penicillamine and triethylenetetramine with copper. J R Soc Med. 1977;70 Supplement 3.

    Google Scholar 

  18. Riha M, Karlickova J, et al. Novel method for rapid copper chelation assessment confirmed low affinity of D-penicillamine for copper in comparison with trientine and 8-hydroxyquinolines. J Inorg Biochem. 2013;123:80–7.

    Article  CAS  PubMed  Google Scholar 

  19. Zheng Z-X, Lin J-M, Qu F, Hobo T. Chiral separation with ligand-exchange micellar electrokinetic chromatography using a D-penicillamine-copper(II) ternary complex as chiral selector. Electrophoresis. 2003;24:4221–6.

    Article  CAS  PubMed  Google Scholar 

  20. Gupta A, Lutsenko S. Human copper transporters: mechanism, role in human diseases and therapeutic potential. Future Med Chem. 2009;1(6):1125–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. De Romana DL, Olivares M, et al. Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol. 2011;25:Iss 1.

    Article  Google Scholar 

  22. Turnlund JR. Human whole-body copper metabolism. Am J Clin Nutr. 1998;67:960S–4.

    CAS  PubMed  Google Scholar 

  23. Birker PJMWL, Freeman HC. Structure, properties, and function of a Copper (I)-Copper (II) Complex of D-Penicillamine: pentathallium (I) μȢ-Chloro-dodeca (D-penicillaminato)-octacuprate(I)hexacuprate(II) n-hydrate. J Am Chem Soc. 1977;99:21.

    Google Scholar 

  24. Sisombath NS, et al. Lead (II) binding to the chelating agent d-penicillamine in aqueos solution. Inorg Chem. 2014;53(23):12459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Margaret SE. Chelation: harnessing and enhancing heavy metal detoxification – a review. Sci World J. 2013;2013:219840.

    Google Scholar 

  26. Troger W, and the Isolde Collaboration. Hg(II) coordination studies in penicillamine enantiomers by 199mHg-TDPAC. Hyperine Interact. 2001;136/137:673–80.

    Article  Google Scholar 

  27. Peterson RG, Rumack BH. D-penicillamine therapy of acute arsenic poisoning. J Pediatr. 1977;91(4):661.

    Article  CAS  PubMed  Google Scholar 

  28. Pinto B, Goyal P, Flora SJS, Gill KD, Singh S. Chronic arsenic poisoning following ayurvedic medication. J Med Toxicol. 2014;10(4):395–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kreppel H, Reichl FX, Forth W, Fichtl B. Lack of effectiveness of D-penicillamine in experimental arsenic poisoning. Vet Hum Toxicol. 1989;31(1):1–5.

    CAS  PubMed  Google Scholar 

  30. Andersen O. Principles and recent developments in chelation treatment of metal intoxication. Chem Rev. 1999;99:2683–710.

    Article  CAS  PubMed  Google Scholar 

  31. Pinter R, Hoge WA, McPherson E. Infant with severe penicillamine embryopathy born to a woman with Wilson Disease. Am J Med Genet. 2004;128A:294–8.

    Article  CAS  PubMed  Google Scholar 

  32. Carey JC, et al. Determination of human teratogenicity by the astute clinician method: review of illustrative agents and a proposal of guidelines. Birth Defects Res (Part A). 2008;85:63–8.

    Article  Google Scholar 

  33. Bennett WM, Aronoff GR, Golper TA, et al. Drug prescribing in renal failure. Philadelphia: American College of Physicians; 1987.

    Google Scholar 

  34. Matthey F, Perrett D, Greenwood RN, et al. The use of D-penicillamine in patients with rheumatoid arthritis undergoing hemodialysis. Clin Nephrol. 1986;25:268–71.

    CAS  PubMed  Google Scholar 

  35. Golding J, Day AT, Wilson MA. Effect of penicillamine after gold treatment. Br Med J. 1978;1(6116):858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Webley M, Coomes EN. An assessment of penicillamine therapy in rheumatoid arthritis and the influence of previous gold therapy. J Rheumatol. 1979;6(1):20–4.

    CAS  PubMed  Google Scholar 

  37. Kean WF, et al. Prior gold therapy does not influence the adverse effects of D-penicillamine in rheumatoid arthritis. Arthritis Rheum. 1982;25(8):917–22.

    Article  CAS  PubMed  Google Scholar 

  38. Aaron S, Davis P, Biggs D. D-penicillamine does not chelate gold. J Rheumatol. 1984;11(6):869.

    CAS  PubMed  Google Scholar 

  39. American Academy of Pediatrics, Committee on Drugs. Treatment guidelines for lead exposure in children. Pediatrics. 1995;96:155–60.

    Google Scholar 

  40. Micromedex, Truven Health Analytics Inc. 2016

    Google Scholar 

  41. Kosnett MJ, Wedeen RP, Rothenberg S, et al. Recommendations for medical management of adult lead exposure. Environ Health Perspect. 2007;115(3):463–71.

    Article  CAS  PubMed  Google Scholar 

  42. Dart RC, Hurlburt KM, Boyer-Hassen LV, et al. Lead. In: Dart RC, Caravati EM, McCuigan MA, editors. Medical toxicology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2004. p. 1423–31.

    Google Scholar 

  43. Sunil H, et al. Diagnosis, evaluation, and treatment of lead poisoning in general population. Indian J Clin Biochem. 2011;26(2):197–201.

    Article  Google Scholar 

  44. Shannon M, Grace A, Graef JW. Use of penicillamine in children with small lead burdens. N Engl J Med. 1989;321:979–80.

    CAS  PubMed  Google Scholar 

  45. Shannon M, Graef J, Lovejoy Jr FH. Efficacy and toxicity of D-penicillamine in low-level lead poisoning. J Pediatr. 1988;112(5):799–804.

    Article  CAS  PubMed  Google Scholar 

  46. Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J. 1992;6(7):2472–6.

    CAS  PubMed  Google Scholar 

  47. Kojima S, Shimada H, Kiyozumi M. Comparative effects of chelating agents on distribution, excretion, and renal toxicity of inorganic mercy in rats. Res Commun Chem Pathol Pharmacol. 1989; 64(3) 471–84.

    Google Scholar 

  48. Abbaslou P, Zaman T. A Child with elemental mercy poisoning and unusual brain MRI findings. Clin Toxicol. 2006;44(1):85–8.

    Article  Google Scholar 

  49. Khodashenas E, Aelami M, Balali-Mood M. Mercury poisoning in two 13-year-old twin sisters. J Res Med Sci. 2015;20(3):308–11.

    PubMed  PubMed Central  Google Scholar 

  50. Sathe K, Ali U, Ohri A. Acute renal failure secondary to ingestion of ayurvedic medicine containing mercury. Indian J Nephrol. 2013;23(3):301–3.

    CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Pharmacology and Toxicology, Children’s Mercy Hospital Kansas City, Kansas City, MO, USA

    Cristy Eidelman

  2. Section of Toxicology Pediatrician, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA

    Jennifer A. Lowry

Authors
  1. Cristy Eidelman
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  2. Jennifer A. Lowry
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Corresponding author

Correspondence to Jennifer A. Lowry .

Editor information

Editors and Affiliations

  1. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Jeffrey Brent

  2. Office of New Drugs Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas' Hospital, London, United Kingdom

    Paul Dargan

  4. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Benjamin Hatten

  5. Med & Toxicological Intensive Care Unit, Lariboisière Hospital Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. University of Colorado School of Medicine, Toxicology Associates, Denver, Colorado, USA

    Robert Palmer

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies, and case reports, or reports of expert committees.

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Eidelman, C., Lowry, J.A. (2016). D-Penicillamine. In: Brent, J., Burkhart, K., Dargan, P., Hatten, B., Megarbane, B., Palmer, R. (eds) Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-20790-2_182-1

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  • DOI: https://doi.org/10.1007/978-3-319-20790-2_182-1

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  • Publisher Name: Springer, Cham

  • Online ISBN: 978-3-319-20790-2

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