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Azelaic Acid

A Review of its Pharmacological Properties and Therapeutic Efficacy in Acne and Hyperpigmentary Skin Disorders

Summary

Synopsis

Azelaic acid is a naturally occurring saturated dicarboxylic acid which, on topical application (usually as a 20% cream), has been shown to be effective in the treatment of comedonal acne and inflammatory (papulopustular, nodular and nodulocystic) acne, as well as various cutaneous hyperpigmentary disorders characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna. In addition, azelaic acid has an antiproliferative and cytotoxic effect on the human malignant melanocyte, and preliminary findings indicate that it may arrest the progression of cutaneous malignant melanoma. The mechanism of this selective cytotoxic action of azelaic acid is unclear, but may possibly be related to its inhibition of mitochondrial oxidoreductase activity and DNA synthesis. In controlled studies, topical azelaic acid demonstrated comparable antiacne efficacy to topical tretinoin, benzoyl peroxide, erythromycin and oral tetracycline, while in patients with melasma azelaic acid proved at least as effective as topical hydroquinone. On topical application azelaic acid is well tolerated, with adverse effects apparently limited to a generally mild and transient local cutaneous irritation. Thus, topical azelaic acid, employed either as monotherapy or in combination with other treatments, is likely to prove of value in the management of acne and several hyperpigmentary disorders, most notably melasma.

Pharmacodynamic Studies

Azelaic acid displays bacteriostatic and bactericidal properties against a variety of aerobic and anaerobic microorganisms present on acne-bearing skin. Topical application of 20% azelaic acid cream caused marked reductions in the densities of cutaneous micrococcaceae and intrafollicular Propionibacterium sp., and decreased the free fatty acid content of skin surface lipids. Sebum production, sebum composition and sebaceous gland morphology were not significantly altered.

In vitro, azelaic acid 20 to 50 mmol/L displayed a time- and concentration-dependent antiproliferative effect on normal human and neonatal mouse keratinocytes, mouse melanoma cells and human cutaneous and choroidal melanoma cells; a cytotoxic effect was manifest at concentrations greater than 40 mmol/L. A similar antiproliferative/cytotoxic effect has been demonstrated with human lymphoma- and leukaemia-derived cell lines and squamous carcinoma cells.

Topical 20% azelaic acid cream showed an antikeratinising effect on normal and acne-affected skin which was related to decreased synthesis of filaggrin (keratin filament aggregating protein); hence a reduction in follicular hyperkeratosis may partly underlie the drug’s anti-acne action. Azelaic acid appears to act selectively on hyperactive and abnormal melanocytes. On prolonged (≤ 3 months) topical application, 15 or 20% azelaic acid cream caused no appreciable depigmentation of normally pigmented human skin, freckles, senile lentigines or naevi, but reduced epidermal melanogenesis in patients with lentigo maligna. Combined topical and oral (10 to 15 g/day) azelaic acid therapy in patients with cutaneous malignant melanoma resulted in the degeneration and disappearance of malignant epidermal melanocytes.

The antiproliferative/cytotoxic effects of azelaic acid appear to be mediated primarily via disruption of mitochondrial respiration and/or cellular DNA synthesis, rather than via inhibition of tyrosinase activity. Ultrastructural studies demonstrated selective and marked mitochondrial swelling and vacuolation, and accumulation of cytoplasmic lipid droplets, both in cutaneous/ choroidal melanoma cells exposed to azelaic acid (≤ 100 mmol/L) in vitro and in skin biopsies obtained from patients with lentigo maligna or cutaneous melanoma treated with topical azelaic acid. Differences in cellular permeability and/or metabolic activity may account for the greater susceptibility of hyperactive and abnormal epidermal cells (keratinocytes and melanocytes) to the antiproliferative and depigmenting actions of azelaic acid.

Pharmacokinetic Studies

Azelaic acid has been administered to humans orally, by intravenous, intra-arterial and intralymphatic infusion ( 15% solution of the disodium salt) and topically (usually as 20% azelaic acid cream). In healthy volunteers, plasma azelaic acid concentrations peaked at 6 to 75 mg/L 2 hours after a single oral dose of 0.5 to 5g. Plateau plasma azelaic acid concentrations in excess of 940 mg/L (consistent with those showing antiproliferative effects in vitro) have been achieved with continuous intravenous/intra-arterial infusion. Percutaneous absorption of azelaic acid is governed by the formulation employed, varying from 3% (ointment or emulsion base) to 8% (gel) of the administered dose. In humans, azelaic acid is partially metabolised by mitochondrial β-oxidation to acetyl CoA and malonyl CoA; unchanged drug is excreted exclusively in the urine.

Therapeutic Efficacy

Under controlled conditions, twice daily topical application of 20% azelaic acid cream was markedly more effective than that of its vehicle in reducing numbers of comedones, papules and pustules in patients with mild-to-moderate acne. On completion of 3 months’ therapy, a significantly higher proportion of patients with papulopustular acne had achieved a good-to-excellent clinical response with azelaic acid (64%) than with vehicle (36%). Over 5- or 6-month treatment periods, topical 20% azelaic acid cream, applied twice daily, was of comparable efficacy to topical 0.05% tretinoin cream, topical 5% benzoyl peroxide gel, topical 2% erythromycin cream, and oral tetracycline 0.5 to 1.0 g/day in comedonal and mild-to-moderately severe inflammatory acne, producing a good-to-excellent clinical response in 65 to 80% of patients with mild-to-moderate acne and in approximately 60% of those with moderate-to-severe acne. However, topical 20% azelaic acid, administered twice daily over a 6-month period, was significantly less effective than oral isotretinoin 0.5 to 1.0 mg/kg/day in conglobate acne. Differences in the time course of the responses to azelaic acid and the various anti-acne agents included a slightly more rapid initial improvement in papulopustular acne with benzoyl peroxide.

Preliminary findings indicate that topical 20% azelaic acid cream, administered twice daily over a 6-month treatment period, is of comparable efficacy to topical 4% hydroquinone cream, and significantly superior to 2% hydroquinone cream, in reducing pigmentation and lesion size in melasma (good-to-excellent clinical response in 73 vs 19% of patients receiving azelaic acid and 2% hydroquinone, respectively).

The clinical response to topical 15 or 20% azelaic acid cream, applied twice daily for periods of 3 to 12 months, in lentigo maligna was characterised by a progressive reduction in pigmentation, flattening of indurated lesion surfaces and apparent lesion shrinkage. Although response rates showed large interstudy variation (ranging from 13 to 100%), clinical remission, once achieved, was sustained. This inconsistency of response to azelaic acid would, nevertheless, suggest that its use should be confined to those cases of lentigo maligna in which surgery is contraindicated. Similarly, while preliminary findings indicate that combined topical (20% cream) and oral (10 to 15 g/day) azelaic acid therapy may arrest lesion progression in patients with cutaneous malignant melanoma, surgical excision must remain the accepted mode of treatment for this condition. Other possible indications for azelaic acid include treatment of physical and phototoxic hyperpigmentation.

Adverse Effects

Azelaic acid, at oral doses of up to 4000 mg/kg, has shown no evident toxicity, teratogenicity or mutagenicity in animal studies, and during oral (≤ 20 g/day) or topical (20% cream) administration to humans has demonstrated no systemic adverse effects. Local cutaneous irritation, marked by erythema, pruritus, scaling and a burning sensation, occurs in 5 to 10% of patients (an incidence comparable to that seen with its cream base), and is mild and transient, generally subsiding after 2 to 4 weeks of treatment. In terms of local cutaneous effects, topical azelaic acid is well tolerated in comparison with standard topical anti-acne agents and, in addition, is free of the specific systemic effects variously associated with oral anti-acne agents: antibiotic resistance (tetracycline), mucocutaneous effects and teratogenicity (isotretinoin), potential endocrine imbalance (cyproterone acetate). The incidences of local cutaneous irritation associated with the use of topical 20% azelaic acid and 2 to 4% hydroquinone creams appear comparable.

Dosage and Administration

The topical route of administration is the only one currently available for azelaic acid. A 20% azelaic acid cream applied twice daily is most frequently employed.

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References

  1. Akamatsu H, Miyachi Y, Komura J. Effect of azelaic acid on neutrophil function: a possible cause for its efficacy in treating pathogenetically unrelated diseases. Archives of Dermatological Research, in press, 1991

  2. Balina LM, Borelli SS, Di Paola A. 20% azelaic acid cream in the treatment of melasma: a double-blind controlled comparison with 4% hydroquinone cream. International Journal of Dermatology, in press, 1991

  3. Bargoni N, Tazartes O. On the effect of aliphatic saturated dicarboxylic acids on anaerobic glycolysis in chicken embryo. Italian Journal of Biochemistry 32: 385–390, 1983

    PubMed  CAS  Google Scholar 

  4. Bladon PT, Burke BM, Cunliffe WJ, Förster RA, Holland KT, et al. Topical azelaic acid and the treatment of acne: a clinical and laboratory comparison with oral tetracycline. British Journal of Dermatology 114: 493–499, 1986

    PubMed  Article  CAS  Google Scholar 

  5. Bojar RA. The in vitro antimicrobial effects of azelaic acid upon cutaneous microorganisms, Ph.D Thesis, University of Leeds, 1990

    Google Scholar 

  6. Bojar RA, Holland KT, Leeming JP, Cunliffe WJ. Azelaic acid: its uptake and mode of action in Staphylococcus epidermidis NCTC 11047. Journal of Applied Bacteriology 64: 497–504, 1988

    PubMed  Article  CAS  Google Scholar 

  7. Breathnach AS. Azelaic acid-biological activities and therapeutic applications. Drugs of Today 25: 463–472, 1989

    CAS  Google Scholar 

  8. Breathnach AS, Martin B, Nazzaro-Porro M, Passi S, Mann P, et al. Effects of dicarboxylic acids on normal human melanocytes in dispersed tissue culture. British Journal of Dermatology 101: 641–649, 1979

    PubMed  Article  CAS  Google Scholar 

  9. Breathnach AS, Nazzaro-Porro M, Passi S. Azelaic acid. British Journal of Dermatology 111: 115–120, 1984

    PubMed  Article  CAS  Google Scholar 

  10. Breathnach AC, Nazzaro-Porro M, Passi S, Zina G. Azelaic acid therapy in disorders of pigmentation. Clinics in Dermatology 7: 106–119, 1989a

    PubMed  Article  CAS  Google Scholar 

  11. Breathnach AS, Robins EJ, Bhasin Y, Ethridge L, Nazzaro-Porro M, et al. Observations on cell kinetics and viability of a human melanoma cell line exposed to azelaic acid. Histology and Histopathology 1: 235–240, 1986

    PubMed  CAS  Google Scholar 

  12. Breathnach A, Robins EJ, Bhasin Y, Ethridge L, Nazzaro-Porro M, et al. Scanning electron microscopy of human and murine melanoma cells exposed to medium chain-length carboxylic acids in tissue culture. Histology and Histopathology 2: 291–297, 1987

    PubMed  CAS  Google Scholar 

  13. Breathnach AS, Robins EJ, Nazzaro-Porro M, Passi S, Picardo M. Hyperpigmentary disorders — mechanisms of action: effect of azelaic acid on melanoma and other tumoral cells in culture. Acta Dermato-Venereologica, Suppl. 143: 62–66, 1989b

    CAS  Google Scholar 

  14. Breathnach AS, Robins EJ, Pätzold HC, Bhasin YP, Ethridge LB, et al. Effect of dicarboxylic acids (C6 and C9 ) on human choroidal melanoma in cell culture. Investigative Ophthalmology and Visual Science 30: 491–498, 1989c

    PubMed  CAS  Google Scholar 

  15. Breathnach AS, Ward B, Robins E, Ethridge L. Nazzaro-Porro M, et al. Analytical ultrastructural autoradiographic localization of a dicarboxylic acid in cultured human epidermal cells. Journal of Investigative Dermatology 80: 370, 1983

    Google Scholar 

  16. Cavicchini S, Caputo R. Long-term treatment of acne with 20% azelaic acid cream. Acta Dermato-Venereologica, Suppl. 143: 40–44, 1989

    CAS  Google Scholar 

  17. Clark WH, Mastrangelo MJ, Ainsworth AM, Berd D, Bellett RE, et al. Current concepts of the biology of human cutaneous malignant melanoma. Advances in Cancer Research 24: 267–338, 1977

    PubMed  Article  Google Scholar 

  18. Cunliffe WJ, Holland KT. Clinical and laboratory studies on treatment with 20% azelaic acid cream for acne. Acta Dermato-Venereologica, Suppl. 143: 31–34, 1989

    CAS  Google Scholar 

  19. Detmar M, Mayer-da-Silva A, Stadler R, Orfanos CE. Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro Journal of Investigative Dermatology 93: 70–74, 19

  20. Detmar M, Müller K Gassmüller H, Stadler R, Orfanos CE. Effects of azelaic acid on protein synthesis and proliferation of cultured human keratinocytes. In Orfanos et al. (Eds) Dermatology in Five Continents, Proceedings of the XVII World Congress of Dermatology, pp. 1169–1170, Springer, Berlin, 1988

    Google Scholar 

  21. Detmar M, Müller R, Stadler R, Orfanos CE. Dicarbonsäuren hemmen das Wachstum von Keratinozyten in vitro. Hautarzt 37: 625–627, 1986

    PubMed  CAS  Google Scholar 

  22. De Young L, Young JM, Ballaron SJ, Spires DA, Puhvel SM. Intradermal injection of Propionibacterium acnes: a model of inflammation relevant to acne. Journal of Investigative Dermatology, 83: 394–398, 1984

    PubMed  Article  Google Scholar 

  23. Doherty VR, Ashworth J, Cox N. Azelaic acid in lentigo maligna. British Journal of Dermatology 116: 606, 1987

    Article  Google Scholar 

  24. Dousset N, Douste-Blazy L. Transformation de l’acide azélaique en acides gras monocarboxyliques in vivo chez le rat. Biochimie 55: 1279–1285, 1973

    PubMed  Article  CAS  Google Scholar 

  25. Galhaup I. Azelaic acid: mode of action at cellular and subcellular levels. Acta Dermato-Venereologica, Suppl. 143: 75–82, 1989

    CAS  Google Scholar 

  26. Gassmueller H, Graupe K, Orfanos CE. Azelaic acid and sebum excretion rate. British Journal of Dermatology 113: 800–802, 1985

    PubMed  Article  CAS  Google Scholar 

  27. Geier G, Hauschild T, Bauer R, Kreysel HW. Der Einfluss von Azelainsäure auf das Wachstum von Melanomzellkulturen im Vergleich zu Fibroblastenkulturen. Hautarzt 37: 146–148, 1986

    PubMed  CAS  Google Scholar 

  28. Gollnick H. A new therapeutic agent: azelaic acid in acne treatment. Journal of Dermatological Treatment 3: S23–S28 1990

    Article  Google Scholar 

  29. Gollnick H, Graupe K. Azelaic acid for the treatment of acne: comparative trials. Journal of Dermatological Treatment 1: 27–30, 1989

    Article  Google Scholar 

  30. Gollnick H, Mayer da Silva A, Orfanos CE. Effects of azelaic acid on filaggrin, cytokeratins, and on the ultrastructure of human keratinocytes in vivo. Abstract. Journal of Investigative Dermatology 89: 452, 1987

    Google Scholar 

  31. Graupe K, Zaumseil RP. Skinoren-ein neues Lokaltherapeutikum zur Behandlung der Acne vulgaris. In Jahrbuch der Dermatologie, Wissenschaftliche Verlagsgesellschaft Biermann, in press, 1991

  32. Harris HH, Downing DT, Stewart ME, Strauss JS. Sustainable rates of sebum secretion in acne patients and matched normal control subjects. Journal of the American Academy of Dermatology 8: 200–203, 1983

    PubMed  Article  CAS  Google Scholar 

  33. Hjorth N, Graupe K. Azelaic acid for the treatment of acne: a clinical comparison with oral tetracycline. Acta Dermato-Venereologica, Suppl. 143: 45–48, 1989

    CAS  Google Scholar 

  34. Holland KT, Bojar RA. The effect of azelaic acid on cutaneous bacteria. Journal of Dermatological Treatment 1: 17–19, 1989

    Article  Google Scholar 

  35. Holland KT, Bojar RA, Cunliffe WJ. The interaction of azelaic acid with Propionibacterium acnes. Abstract. Journal of Investigative Dermatology 92: 446, 1989

    Google Scholar 

  36. Holland KT, Ingham E, Cunliffe WJ. A review: the microbiology of acne. Journal of Applied Bacteriology 51: 195–215, 1981

    PubMed  Article  CAS  Google Scholar 

  37. Hu F, Mah K, Teramura DJ. Effects of dicarboxylic acids on normal and malignant melanocytes in culture. British Journal of Dermatology 114: 17–26, 1986

    PubMed  Article  CAS  Google Scholar 

  38. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic acid cream in the treatment of acne vulgaris: comparison with vehicle and topical tretinoin. Acta Dermato-Venereologica, Suppl. 143: 35–39, 1989

    CAS  Google Scholar 

  39. King K, Leeming JP, Holland KT, Cunliffe WJ. The effect of azelaic acid on cutaneous microflora in vivo and in vitro. Abstract. Journal of Investigative Dermatology 84: 438, 1985

    Google Scholar 

  40. Leeming JP, Holland KT, Bojar RA. The in vitro antimicrobial effect of azelaic acid. British Journal of Dermatology 115: 551–556, 1986

    PubMed  Article  CAS  Google Scholar 

  41. Leeming JP, Holland KT, Cunliffe WJ. The pathological and ecological significance of microorganisms colonising acne vulgaris comedones. Journal of Medical Microbiology 20: 11–16, 1985

    PubMed  Article  CAS  Google Scholar 

  42. Leeming JP, Holland KT, Cunliffe WJ. The microbial colonization of inflamed acne vulgaris lesions. British Journal of Dermatology 118: 203–208, 1988

    PubMed  Article  CAS  Google Scholar 

  43. Leibl H, Stingl G, Pehamberger H, Korschan H, Konrad K, et al. Inhibition of DNA synthesis of melanoma cells by azelaic acid. Journal of Investigative Dermatology 85, 417–422, 1985

    PubMed  Article  CAS  Google Scholar 

  44. Leyden JJ, McGinley KJ, Mills OH, Kligman AM. Propionibacterium levels in patients with and without acne vulgaris. Journal of Investigative Dermatology 65: 382–384, 1975

    PubMed  Article  CAS  Google Scholar 

  45. Limburg JA, Zettergren JG, Swanson JE, Rizer RL, Johnson SC. Topical effects of 6-methylene progesterone and azelaic acid on hamster ear sebaceous gland lipogenesis and morphology. Abstract. Journal of Investigative Dermatology 92: 472, 1989

    Google Scholar 

  46. Marples RR, Leyden JJ, Stewart RN, Mills OH, Kligman AM. The skin microflora in acne vulgaris. Journal of Investigative Dermatology 62: 37–41, 1974

    PubMed  Article  CAS  Google Scholar 

  47. Marsden JR, Shuster S. The effect of azelaic acid on acne. British Journal of Dermatology 109: 723–724, 1983

    PubMed  Article  CAS  Google Scholar 

  48. Maru U, Michaud P, Garrigue J, Oustrin J, Rouppiac R. Diffusion in vitro et pénétration cutanée de préparations d’acide azélaique: recherche de corrélations. Journal de Pharmacie de Belgique 37: 207–213, 1982

    PubMed  CAS  Google Scholar 

  49. Matsumoto M, Matsumoto I, Shinka T, Kuhara T, Imamura H, et al. Organic acid and acylcarnitine profiles of glutaric aciduria type 1. Acta Paediatrica Japonica 32: 76–82, 1990

    PubMed  Article  CAS  Google Scholar 

  50. Mayer-da-Silva A. Azelaic acid: pharmacology, toxicology and mechanism of action in acne. Journal of Dermatological Treatment 2: 11–15, 1989

    Article  Google Scholar 

  51. Mayer-da-Silva A, Gollnick H, Detmar M, Gassmüller J, Parry A, et al. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin: an in vivo and in vitrostudy. Acta Dermato-Venereologica, Suppl. 143: 20–30, 1989

    CAS  Google Scholar 

  52. Mayer-da-Silva A, Gollnick H, lmcke E, Orfanos CE. Azelaic acid vs. placebo: effects on normal human keratinocytes and melanocytes. Electron microscopic evaluation after long-term application in vivo. Acta Dermato-Venereologica 67: 116–122, 1987

    PubMed  CAS  Google Scholar 

  53. McLean DI, Peter KK. Apparent progression of lentigo maligna to invasive melanoma during treatment with topical azelaic acid. British Journal of Dermatology 114: 685–689, 1986

    PubMed  Article  CAS  Google Scholar 

  54. Mingrone G, Greco AV, Ciardiello A, Passo A, Nazzaro-Porro M. Distribution of radiolabelled azelaic acid in eye membranes and fluids of rabbits. Experimental Pathology 25: 85–88, 1984

    PubMed  Article  CAS  Google Scholar 

  55. Mingrone G, Greco AV, Nazzaro-Porro M, Passi S. Toxicity of azelaic acid. Drugs under Experimental and Clinical Research 9: 447–455, 1983

    CAS  Google Scholar 

  56. Mingrone G, Tacchino RM, Greco AV, Arcieri-Mastromattei E, Marino F, et al. Preliminary studies of a dicarboxylic acid as an energy substrate in man. Journal of Parenteral and Enterai Nutrition 13: 299–305, 1989

    Article  CAS  Google Scholar 

  57. Nazzaro-Porro M. Azelaic acid. Journal of the American Academy of Dermatology 17: 1033–1041, 1987

    PubMed  Article  CAS  Google Scholar 

  58. Nazzaro-Porro M, Passi S. Identification of tyrosinase inhibitors in cultures of Pityrosporum. Journal of Investigative Dermatology 71: 205–208, 1978

    PubMed  Article  CAS  Google Scholar 

  59. Nazzaro-Porro M, Passi S, Balus L, Breathnach A, Martin B, et al. Effect of dicarboxylic acids on lentigo maligna. Journal of Investigative Dermatology 72: 296–305, 1979

    PubMed  Article  CAS  Google Scholar 

  60. Nazzaro-Porro M, Passi S, Breathnach AS, Zina G. 10 years observations on the effect of azelaic acid on lentigo maligna. Abstract. Journal of Investigative Dermatology 87: 438, 1986

    Article  Google Scholar 

  61. Nazzaro-Porro M, Passi S, Picardo M, Breathnach A. Possible mechanism of action of azelaic acid on acne. Abstract. Journal of Investigative Dermatology 84: 451, 1985

    Google Scholar 

  62. Nazzaro-Porro M, Passi S, Picardo M, Breathnach A, Clayton R, et al. Beneficial effect of 15% azelaic acid cream on acne vulgaris. British Journal of Dermatology 109: 45–48, 1983

    PubMed  Article  CAS  Google Scholar 

  63. Nazzaro-Porro M, Passi S, Zina G, Bernengo A, Breathnach A, et al. Effect of azelaic acid on human malignant melanoma. Lancet 1: 1109–1111, 1980

    PubMed  Article  CAS  Google Scholar 

  64. Nazzaro-Porro M, Passi S, Zina G, Breathnach AS. Ten years’ experience of treating lentigo maligna with topical azelaic acid. Acta Dermato-Venereologica, Suppl. 143: 49–57, 1989

    CAS  Google Scholar 

  65. Niwa T, Ohki T, Maeda K, Saito A, Kobayashi K. Pattern of aliphatic dicarboxylic acids in uremic serum including a new organic acid, 2,4-dimethyladipic acid. Clinica Chimica Acta, 99: 71–83, 1979

    Article  CAS  Google Scholar 

  66. Nüssgen AI, Fritz U, Graupe K, Breitbart E, Schmiegelow P. Topographical analysis of proliferation ([3 H]thymidine labelling index and mitotic index) as compared with tumour growth and tumour weight in xenotransplanted melanoma: changes due to local and systemic application of azelaic acid. Acta Dermato-Verereologica, Suppl.143: 67–74, 1989

    Google Scholar 

  67. Passi S, Nazzaro-Porro M, Picardo M, Mingrone G, Fasella P. Metabolism of straight saturated medium chain length (C9 to C12) dicarboxylic acids. Journal of Lipid Research 24: 1140–1147, 1983

    PubMed  CAS  Google Scholar 

  68. Passi S, Picardo M, De Luca C, Breathnach AS, Nazzaro-Porro M. Scavenging activity of azelaic acid on hydroxyl radicals in vitro. Free Radical Research Communications 11: 329–339, 1991a

    PubMed  Article  CAS  Google Scholar 

  69. Passi S, Picardo M, De Luca C, Nazzaro-Porro M, Breathnach AS, et al. Scavenging activity of azelaic acid on hydroxy radicals ‘in vitro’. Abstract. Journal of Investigative Dermatology 95: 482, 1990

    Google Scholar 

  70. Passi S, Picardo M, Mingrone G, Breathnach S, Nazzaro-Porro M. Azelaic acid: biochemistry and metabolism. Acta Dermato-Venereologica, Suppl.143: 8–13, 19

  71. Passi S, Picardo M, Nazzaro-Porro M, Breathnach A, Confaloni AM, et al. Antimitochondrial effect of saturated medium chain length (C8 -C13 ) dicarboxylic acids. Biochemical Pharmacology 33: 103–108, 1984

    PubMed  Article  CAS  Google Scholar 

  72. Passi S, Picardo M, Zompetta C, De Luca C, Breathnach AS, et al. Oxyradicals — scavenging activity of azelaic acid in biological systems. Free Radical Research Communications, in press, 1991b

  73. Pathak MA, Ciganek ER, Wick M, Sober AJ, Farinelli WA, et al. An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent. Journal of Investigative Dermatology 85: 222–228, 1985

    PubMed  Article  CAS  Google Scholar 

  74. Pathak MA, Wick M, Farinelli W, Fitzpatrick TB. Evaluation of azelaic acid on normal skin pigmentation and on the B-16 mouse melanoma. Abstract. Journal of Investigative Dermatology 72: 266, 1979

    Article  Google Scholar 

  75. Pätzold HC, Breathnach AS, Robins EJ, Daridan ME, Bhasin YP, et al. Effect of dicarboxylic acids on a human squamous carcinoma cell line in culture. Histology and Histopathology 4: 167–171, 1989

    PubMed  Google Scholar 

  76. Picardo M, Passi S, Nazzaro-Porro M, Breathnach A. Effect of medium chain length dicarboxylic acids on mitochondrial respiration. Abstract. Journal of Investigative Dermatology 80: 350, 1983

    Google Scholar 

  77. Picardo M, Passi S, Sirianni MC, Fiorilli M, Russo GD, et al. Activity of azelaic acid on cultures of lymphoma and leukemia-derived cell lines, normal resting and stimulated lymphocytes and 3T3 fibroblasts. Biochemical Pharmacology 34: 1653–1658, 1985

    PubMed  Article  CAS  Google Scholar 

  78. Picardo M, Passi S, Zompetta C, De Luca C, Nazzaro-Porro M, et al. Effect of azelaic acid on oxyradical-induced toxicity in cell culture. Abstract. Journal of Investigative Dermatology 95: 483, 1990

    Google Scholar 

  79. Piquero Martin J, Rothe de Arocha J, Loker DB. Estudio clinico doble ciego en el tratamiento del melasma entre àcido azelaico versus hidroquinona. Medicina Cutanea Ibero-Latino-Americana 16: 511–514, 1988

    PubMed  CAS  Google Scholar 

  80. Pochi PE, Strauss JS. Sebum production, casual sebum levels, titratable acidity of sebum, and urinary fractional 17-ketosteroid excretion in males with acne. Journal of Investigative Dermatology 43: 383–388, 1964

    PubMed  CAS  Google Scholar 

  81. Puhvel SM, Amirian DA. Bacterial flora of comedones. British Journal of Dermatology 101: 543–548, 1979

    PubMed  Article  CAS  Google Scholar 

  82. Rach P, Töpert M. Pharmacological investigation of azelaic acid. Abstract. Journal of Investigative Dermatology 86: 327, 1986

    Google Scholar 

  83. Reith RW, Williamson JD, Breathnach AS, Robins EJ, NazzaroPorro M. Inhibition of vaccinia virus replication by azelaic acid. IRCS Medical Science: Clinical Pharmacology and Therapeutics 13: 783–784, 1985

    CAS  Google Scholar 

  84. Rigoni C, Toffolo P, Serri R, Caputo R. Impiego di una crema a base di acido azelaico 20% nel trattamento del melasma. Giornale Italiano di Dermatologia e Venereologica 124: 1–6, 1989

    Google Scholar 

  85. Robins EJ, Breathnach AS, Bennett D, Ward BJ, Bhasin Y, et al. Ultrastructural observations on the effect of azelaic acid on normal human melanocytes and a human melanoma cell line in tissue culture. British Journal of Dermatology 113, 687–697, 1985a

    PubMed  Article  CAS  Google Scholar 

  86. Robins EJ, Breathnach AS, Ward BJ, Bhasin YP, Ethridge L, et al. Effect of dicarboxylic acids on Harding-Passey and Cloudman S91 melanoma cells in tissue culture. Journal of Investigative Dermatology 85: 216–221, 1985b

    PubMed  Article  CAS  Google Scholar 

  87. Rocchiccioli F, Aubourg P, Bougneres PF. Medium- and longchain dicarboxylic aciduria in patients with Zellweger syndrome and neonatal adrenoleukodystrophy. Pediatric Research 20: 62–66, 1986

    PubMed  Article  CAS  Google Scholar 

  88. Sanchez NP, Pathak MA, Sato S, Fitzpatrick TB, Sanchez JL, et al. Melasma: a clinical, light microscopic, ultrastructural and immunofluoresence study. Journal of the American Academy of Dermatology 4: 698–710, 1981

    PubMed  Article  CAS  Google Scholar 

  89. Sansone G, Reisner RM. Differential rates of conversion of testosterone to dihydrotestosterone in acne and in normal human skin — a possible pathogenic factor in acne. Journal of Investigative Dermatology 56: 366–372, 1971

    PubMed  Article  CAS  Google Scholar 

  90. Schallreuter KU, Pittelkow MR, Wood JM. Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells. Abstract. Journal of Investigative Dermatology 88: 397, 1987

    Google Scholar 

  91. Schallreuter KU, Wood JM. Azelaic acid as a competitive inhibitor of thioredoxin reductase in human melanoma cells. Cancer Letters 36: 297–305, 1987

    PubMed  Article  CAS  Google Scholar 

  92. Stamatiadis D, Bulteau-Portois MC, Mowszowicz I. Inhibition of 5-reductase activity in human skin by zinc and azelaic acid. British Journal of Dermatology 119: 627–632, 1988

    PubMed  Article  CAS  Google Scholar 

  93. Strauss JS. The pathogenesis of acne: how might azelaic acid act? Journal of Dermatological Treatment 1: 3–6, 1989

    Article  Google Scholar 

  94. Töpert M, Rach P, Siegmund F. Pharmacology and toxicology of azelaic acid. Acta Dermato-Venereologica, Suppl. 143: 14–19, 1989

    Google Scholar 

  95. Verallo-Rowell VM, Verallo V, Graupe K, Lopez-Villafuerte L, Garcia-Lopez M. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Dermato-Venereologica, Suppl. 143: 58–61, 1989

    CAS  Google Scholar 

  96. Ward BJ, Breathnach AS, Robins EJ, Bhasin Y, Ethridge L, et al. Analytical, ultrastructural, autoradiographic and biochemical studies on [3 H]dicarboxylic acid added to cultures of melanoma cells. British Journal of Dermatology 111: 29–36, 1984

    PubMed  Article  CAS  Google Scholar 

  97. Ward BJ, Breathnach AS, Robins EJ, Bhasin YP, Ethridge L, et al. Effect of L-carnitine on cultured murine melanoma cells exposed to azelaic acid. Journal of Investigative Dermatology 86: 438–441, 1986

    PubMed  Article  CAS  Google Scholar 

  98. Weinstock MA, Sober AJ. The risk of progression of lentigo maligna to lentigo maligna melanoma. British Journal of Dermatology 116: 303–310, 1987

    PubMed  Article  CAS  Google Scholar 

  99. Wilkerson MG, Wilkin JK. Azelaic acid esters do not depigment pigmented guinea pig skin. Archives of Dermatology 126: 252–253, 1990

    PubMed  Article  CAS  Google Scholar 

  100. Willshaw HE, Rubinstein K. Azelaic acid in the treatment of ocular and adnexal malignant melanoma. British Journal of Ophthalmology 67: 54–57, 1983

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Andrew Fitton.

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Various sections of the manuscript reviewed by: A.S. Breathnach, Sherrington School of Physiology, United Medical and Dental Schools of Guy’s and St Thomas’s Hospitals, University of London, London, England; R. Caputo, Istituto di Clinica Dermatologica Prima e Dermatologia Pediatrica, University of Milan, Milan, Italy; M. Detmar, Department of Dermatology, Medical Center Steglitz, Free University of Berlin, Berlin, Federal Republic of Germany; J.W, Kelly, Cabrini Medical Centre, Malvern, Victoria, Australia; L.R. Lever, Department of Dermatology, University of Wales College of Medicine, Cardiff, Wales; J.J Leyden, Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; H.I. Maibach, Department of Dermatology, School of Medicine, University of California at San Francisco, San Francisco, California, USA; M. Nazzaro-Porro, Istituto Dermatologica San Gallicano, Rome, Italy; J,S. Strauss, Department of Dermatology, University of Iowa, Iowa City, Iowa, USA; Y. Ueda, Department of Dermatology, University of Tokyo, Tokyo, Japan.

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Fitton, A., Goa, K.L. Azelaic Acid. Drugs 41, 780–798 (1991). https://doi.org/10.2165/00003495-199141050-00007

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Keywords

  • Acne
  • Tretinoin
  • Azelaic Acid
  • Oral Tetracycline
  • Investigative Dermatology