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Pharmaceutisch Weekblad

, Volume 7, Issue 4, pp 134–140 | Cite as

Ethylenediamine, profile of a sensitizing excipient

  • J. Zuidema
Review Articles

Abstract

Ethylenediamine is an excipient with many industrial and pharmaceutical uses. It is included in creams as a stabilizer and in aminophylline as the counter ion of theophylline. Ethylenediamine is one of the most frequent contact sensitizers, producing local and generalized reactions. Besides, many cases of systemically induced dermatitis have also been described both after oral, rectal and intravenous use. Inhalation of ethylenediamine or aminophylline dust may provoke rhinitis and asthmatic reactions. In contrast to these delayed reactions only one immediate reaction of the urticarial type after intravenous use has been described. Ethylenediamine shows cross-reactions with antihistamines of the ethylenediamine derivative group, with edetate, other amines, piperazine and hydroxyzine. Ethylenediamine shows a short half-life of about 0.55 h and a small volume of distribution of 0.133 l/kg. After oral administration its bioavailability is about 0.34, due to a substantial first-pass effect. Renal excretion of the unchanged substance amounts to only about 18% after intravenous and 3% after oral administration. It behaves independently from theophylline after administration of aminophylline. Good alternatives are now available for the pharmaceutical applications of ethylenediamine. Theophylline itself is well absorbed orally; for the intravenous administration theN-methylglucamine salt is sufficiently soluble. Suppositories containing pure theophylline are commercially available in some countries, but the experience with this product is relatively small.

Keywords

Theophylline Dermatitis Rhinitis Ethylenediamine Piperazine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Elias JA, Levinson I. Hypersensitivity reactions to aminophylline. Am Rev Respir Dis 1981;123:550–2.PubMedGoogle Scholar
  2. 2.
    Cotgreave IA, Caldwell J. Comparative plasma pharmacokinetics of theophylline and ethylenediamine after administration of aminophylline to man. J Pharm Pharmacol 1983;35:378–82.PubMedGoogle Scholar
  3. 3.
    Turner A, Osol A. The spectrophotometric determination of the dissociation of theophylline. J Am Pharm Assoc [Sci] 1949;38:158.Google Scholar
  4. 4.
    Yevstratova KI, Ivanova AI. Dissociation constants and methods for analyses of some organic bases. (In Russian.) Farmaciya 1968;17:41.Google Scholar
  5. 5.
    Cotgreave IA, Caldwell J. Physicochemical andin vitro biological studies on the possible association between theophylline and ethylenediamine in solution. J Pharm Pharmacol 1983;35:774–9.PubMedGoogle Scholar
  6. 6.
    Tashma Z. NMR study of theophylline-ethylenediamine interactions in aqueous solution. J Pharm Pharmacol 1984;36:758–60.PubMedGoogle Scholar
  7. 7.
    Zuidema J. Physical and chemical properties of xanthine derivatives. In: Merkus FWHM, Hendeles L, eds. Sustained release theophylline. Amsterdam: Excerpta Medica, 1983:11–27.Google Scholar
  8. 8.
    White MI, Douglas WS, Main RA. Contact dermatitis attributed to ethylenediamine. Br Med J 1978;1:415–6.PubMedGoogle Scholar
  9. 9.
    Eriksen KE. Allergy to ethylenediamine. Arch Dermatol 1975;111:791.CrossRefGoogle Scholar
  10. 10.
    Tas J, Weissberg D. Allergy to aminophylline. Acta Allergol 1958;12:39–42.PubMedGoogle Scholar
  11. 11.
    Baer RL, Cohen HJ, Neidorff AH. Allergic eczematous sensitivity to aminophylline. Arch Dermatol 1959;79:647–8.Google Scholar
  12. 12.
    Eberhartiger C. Kontaktallergie gegen äthylendiamin. Hautarzt 1964;15:450–1.PubMedGoogle Scholar
  13. 13.
    Epstein E, Maibach HJ. Ethylenediamine. Arch Dermatol 1968;98:476–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Hjorth N. Dermatitis from ethylenediamine. Contact Dermatitis Newsletter 1969;5:107.Google Scholar
  15. 15.
    Maibach H, Epstein E. Ethylenediamine sensitivity. Contact Dermatitis Newsletter 1971;9:207.Google Scholar
  16. 16.
    Fisher AA. The broad implications of allergic sensitization to ethylenediamine hydrochloride. Contact Dermatitis Newsletter 1973;14:418–23.Google Scholar
  17. 17.
    Cronin E. Contact dermatitis. Edinburgh: Churchill Livingstone, 1980.Google Scholar
  18. 18.
    Dooms-Goossens A. Allergic contact dermatitis to ingredients used in topically applied pharmaceutical products and cosmetics. Leuven: Catholic University of Leuven, 1982. Dissertation.Google Scholar
  19. 19.
    Fisher AA. Ethylenediamine dermatitis. Arch Dermatol 1969;100:519–20.CrossRefPubMedGoogle Scholar
  20. 20.
    Van Hecke E. Ethylenediamine sensitivity from exposure to epoxy resin hardeners and MycologsR cream. Contact Dermatitis 1975;1:344–8.PubMedGoogle Scholar
  21. 21.
    Provost TT, Jillson OF. Ethylenediamine contact dermatitis. Arch Dermatol 1967;96:231–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Fisher AA. Contact dermatitis. Philadelphia: Lea and Febiger, 1973.Google Scholar
  23. 23.
    De Shazo RD, Stevenson HC. Generalized dermatitis to aminophylline. Ann Allergy 1981:46:152–5.PubMedGoogle Scholar
  24. 24.
    Hardy C, Schofield O, George CF. Allergy to aminophylline. Br Med J 1983;286:2051–2.Google Scholar
  25. 25.
    Petrozzi JW, Shore RN. Generalized exfoliative dermatitis from ethylenediamine. Arch Dermatol 1976;112:525–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Bernstein JE, Lorincz AL. Ethylenediamine-induced exfoliative erythroderma. Arch Dermatol 1979;115:360–1.CrossRefPubMedGoogle Scholar
  27. 27.
    Van den Berg WHHW, Van Ketel WG. Contactallergie voor ethyleendiamine. Ned Tijdschr Geneeskd 1983;127:1801–2.PubMedGoogle Scholar
  28. 28.
    Lawyer CH, Bardana EJ, Rodgers R, Gerber N. Utilization of intravenous dihydroxypropyltheophylline in an aminophylline-sensitive patient, and its pharmacokinetic comparison with theophylline. J Allergy Clin Immunol 1980;65:353–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Booth BH, Coleman WP, Mitchell DQ. Urticaria following intravenous aminophylline. Ann Allergy 1979;43:289–90.PubMedGoogle Scholar
  30. 30.
    Lam S, Chan-Yeung M. Ethylenediamine-induced asthma. Am Rev Respir Dis 1980;121:151–5.PubMedGoogle Scholar
  31. 31.
    Fisher AA. Allergic paraben and benzylalcohol hypersensitivity relationship of the ‘delayed’ and ‘immediate’ varieties. Contact Dermatitis 1975;1:281–4.PubMedGoogle Scholar
  32. 32.
    Wong D, Lopapa AF, Haddad ZH. Immediate hypersensitivity reaction to aminophylline. J Allergy Clin Immunol 1971;48:165–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Fisher AA. Instructions for the ethylenediamine-sensitive patient. Cutis 1974;13:27–8.Google Scholar
  34. 34.
    White MI. Contact Dermatitis from ethylenediamine. Contact Dermatitis 1978;4:291–3.PubMedGoogle Scholar
  35. 35.
    Calnan CD. Occupational piperazine Dermatitis. Contact Dermatitis 1975;1:126.Google Scholar
  36. 36.
    Burry JN. Ethylenediamine sensitivity with a systemic reaction to piperazine citrate. Contact Dermatitis 1978;4:380.PubMedGoogle Scholar
  37. 37.
    Wright S, Harman RRH. Ethylenediamine and piperazine sensitivity. Br Med J 1983;287:463–4.Google Scholar
  38. 38.
    Rudzki E, Krajenska D. Cross-reactions between ethylenediamine, diethylenetriamine and triethylenetetramine. Contact Dermatitis 1976;2:311–3.PubMedGoogle Scholar
  39. 39.
    Epstein E. Negative patchtests to ethylenediaminetetra-acetate in patients allergie to ethylenediamine. Contact Dermatitis Newsletter 1974;16:475.Google Scholar
  40. 40.
    Raymond JZ, Gross PR. EDTA: preservative dermatitis. Arch Dermatol 1969;100:436.CrossRefPubMedGoogle Scholar
  41. 41.
    Caldwell J, Cotgreave IA. Comparative disposition of theophylline and ethylenediamine given as aminophylline to human volunteers. Br J Clin Pharmacol 1982;14:610 P.Google Scholar
  42. 42.
    Caldwell J, Cotgreave IA. Verteilung von Theophyllin and Ethylendiamin verabreicht als Theophyllin-Ethylendiamin bei Probanden. Therapiewoche 1983;33:969–76.Google Scholar
  43. 43.
    Caldwell J, Cotgreave IA. An HPLC assay for ethylenediamine in plasma and urine. Br J Pharmacol 1982;77:419P.Google Scholar
  44. 44.
    Caldwell J, Cotgreave IA. The metabolism of ethylenediamine in the rat. Br J Pharmacol 1983;78:62 P.Google Scholar
  45. 45.
    Markiw RT. Isolation ofN-acetylethylenediamine from urine of patients on Amesec. Biochem Med 1975;14:152–5.CrossRefPubMedGoogle Scholar
  46. 46.
    McGinity JW, Brown RL. Stabilizing effect of inorganic phosphate salts on antibiotic-steroid ophthalmic preparations. J Pharm Sci 1975;64:1528–30.PubMedGoogle Scholar
  47. 47.
    Bülow KB, Larsson H, Leideman T. Plasma level and broncholytic effect of choline theophyllinate after a single dose of a press-coated tablet formulation. Eur J Clin Pharmacol 1975;8:115–8.CrossRefPubMedGoogle Scholar
  48. 48.
    Jonkman JHG, Holtkamp-Zieleman MB, Hoff-van den Berg EM, Grimberg N, Schoenmaker R. Oploskarakteristieken van enkele cholinetheofyllinaattabletten. Pharm Weekbl 1981;116:665–71.Google Scholar
  49. 49.
    Curtis GH, Crawford PF. Cutaneous sensitivity to monoglycerol para-aminobenzoate. Cleve Clin Q 1951;35–40.Google Scholar
  50. 50.
    Martindale. The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982.Google Scholar
  51. 51.
    Zuidema J, Merkus FWHM. Chemical and biopharmaceutical aspects of theophylline and its derivatives. Curr Med Res Opin 1979;6:14S-25S.Google Scholar
  52. 52.
    French IW, Mildon CA. The pharmacokinetics of theophylline. Curr Med Res Opin 1979;6:3S-13S.Google Scholar
  53. 53.
    Tukker JJ, De Blaey CJ. Prolonged storage of aminophylline suppositories. Pharm Weekbl [Sci] 1984;6:96–8.Google Scholar
  54. 54.
    FNA. Formulary of the Dutch Pharmacists. The Hague: Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie, 1979.Google Scholar
  55. 55.
    Zuidema J, Merkus FWHM. Pharmacokinetics and pharmacodynamics of diprophylline. Pharm Weekbl [Sci] 1981;3:216–21.Google Scholar
  56. 56.
    Monks TJ, Smith RL, Caldwell J. A metabolic and pharmacokinetic comparison of theophylline and aminophylline. J Pharm Pharmacol 1981;33:93–7.PubMedGoogle Scholar
  57. 57.
    Caldwell J, Monks TJ, Smith RL. A comparison of the metabolism and pharmacokinetics of intravenously administered theophylline and aminophylline in man. Br J Pharmacol 1978;63:369P-70P.Google Scholar
  58. 58.
    Caldwell J, Cotgreave IA. Plasma protein binding and distribution in the blood of theophylline and aminophylline. Br J Pharmacol 1981;74:876–7P.Google Scholar
  59. 59.
    Aslaksen A, Bakke OM, Vigander T. Comparative pharmacokinetics of theophylline and aminophylline in man. Br J Clin Pharmacol 1981;11:269–73.PubMedGoogle Scholar
  60. 60.
    Zimmerman I, Schulz HU, Ulmer WT. Blutspiegelverlauf bei intravenöser, intramuskulärer und oraler Gabe von Theophyllin-aethylendiamin und neutral gelöstem Theophyllin. Arzneim Forsch 1978;28:1652–4.Google Scholar
  61. 61.
    Baccouche M, Dittman EC, Eltze M, Kilian U. Ethylendiamine —Pharmakologie von Aethylendiamin und dessen Wechselwirkung mit Theophyllin. Prax Klin Pneumol 1983;37:322–5.PubMedGoogle Scholar
  62. 62.
    Stone TW, Perkins MN. Ethylenediamine as a GABA-mimetic. TIPS 1984;241–3.Google Scholar
  63. 63.
    Greif N. Cutaneous safety of fragrance material as measured by the maximization test. Am Perf and Cosm 1967;82:54–7.Google Scholar

Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • J. Zuidema
    • 1
  1. 1.Department of BiopharmaceuticsUniversity of AmsterdamTV AmsterdamThe Netherlands

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