Advertisement

Pharmaceutisch Weekblad

, Volume 14, Issue 2, pp 33–37 | Cite as

Acitretin (Neotigason®)

A review of pharmacokinetics and teratogenicity and hypothesis on metabolic pathways
  • M. L. Bouvy
  • M. C. J. M. Sturkenboom
  • M. C. Cornel
  • L. T. W. De Jong-Van den Berg
  • B. H. C. Stricker
  • H. Wesseling
Reviews

Abstract

Acitretin was introduced as a replacement for etretinate, the ethyl ester of acitretin. Acitretin is eliminated at a much faster rate than etretinate. Although both drugs are teratogens, the replacement was important especially as it allowed for a much shorter post-medication period in which pregnancy should be precluded. Recent findings showed the presence of etretinate in the plasma of acitretin-treated patients. This article gives a review of known metabolic pathways of the retinoids and tries to elucidate the possible conversion of acitretin into etretinate after acitretin ingestion.

Keywords

Acitretin Etretinate Metabolism Pharmacokinetics Retinoids Teratogens 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Orfanos CE, Ehlert R, Gollnick H. The retinoids. A review of their clinical pharmacology and therapeutic use. Drugs 1987;34:459–503.PubMedGoogle Scholar
  2. 2.
    Peck GL. Retinoids. Therapeutic use in dermatology. Drugs 1982;24:341–51.PubMedGoogle Scholar
  3. 3.
    Gollnick H. Acitretin in psoriasis. An update. In: Saurat JH, ed. Retinoids: 10 years on. Basle: Karger, 1991:204–13.Google Scholar
  4. 4.
    Leyden JJ, McGinley KJ. Effect of 13-cis-retinoic acid on sebum production andPropionibacterium acnes in severe nodulocystic acne. Arch Dermatol Res 1982;272:331–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Happle R, Van de Kerkhof PCM, Traupe H. Retinoids in disorders of keratinisation. Their use in adults. Dermatologica 1987;175 Suppl 1:107–24.PubMedGoogle Scholar
  6. 6.
    Slack JMW. We have a morphogen. Nature 1987;327:553–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Thaller C, Eichele G. Identification and spatial distribution of retinoids in the developing chick limb bud. Nature 1987;327:625–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Dencker L, Annerwall E, Eriksson U, Busch C. Is the cellular retinoic acid binding protein (CRABP) important for normal and abnormal craniofacial development? Teratology 1989;40:272–4.Google Scholar
  9. 9.
    Löfberg B, Chahoud I, Bochert G, Nau H. Teratogenicity of the 13-cis and 11-trans-isomers of the aromatic retinoid atretin. Correlation to transplacental pharmacokinetics in mice during organogenesis after a single oral dose. Teratology 1990;41:707–16.CrossRefPubMedGoogle Scholar
  10. 10.
    Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, et al. Retinoic acid embryopathy. N Engl J Med 1985;313:837–41.PubMedGoogle Scholar
  11. 11.
    De Wals P. Surveillance of retinoic acid embryopathy. Teratology 1989;40:274.Google Scholar
  12. 12.
    Ayme S, Julian C, Gambarelli D, Mariotti B, Maurin N. Isotretinoin dose and teratogenicity. Lancet 1988;1:655.CrossRefGoogle Scholar
  13. 13.
    Rollman O, Vahlquist A. Retinoids concentrations in skin serum and adipose tissue of patients treated with etretinate. Br J Dermatol 1983;109:439–47.PubMedGoogle Scholar
  14. 14.
    Vahlquist A, Rollman O, Pihl-Lundin I. Tissue distribution of aromatic retinoid (etretinate) in three autopsy cases. Drug accumulation in adrenal and fat. Acta Derm Venerol 1986;66:431–4.PubMedGoogle Scholar
  15. 15.
    Gollnick H, Rinck G, Bitterling T, Orfanos CE. Pharmacokinetik von Etretinat, Acitretin und 13-cis-Acitretin: neue Ergebnisse und Nutzen der Blutspiegel-orientierten klinischen Anwendung. Z Hautkrankh 1990;65(1):40–50.Google Scholar
  16. 16.
    Larsen FG, Jacobsen P, Larsen CG, Kragballe K, Nielsen-Kudsk F. Pharmacokinetics of etretin and etretinate during long-term treatment of psoriasis patients. Pharmacol Toxicol 1988;62:159–65.PubMedGoogle Scholar
  17. 17.
    Paravicini U. Pharmacokinetics and metabolism of etretinate and isotretinoin. In: Roenigk HH, Maibach HI, eds. Psoriasis. New York: Marcel Dekker, 1985:523–35.Google Scholar
  18. 18.
    Massarella J, Vane F, Buggé C, Rodriguez L, Cunningham WH, Franz T, Colburn W. Etretinate kinetics during chronic dosing in severe psoriasis. Clin Pharmacol Ther 1985;37:439–46.PubMedGoogle Scholar
  19. 19.
    Berbis P, Bun H, Al Mallah NR, Durand A, Rognin C, Geiger JM, Privat Y. Residual plasma concentrations of acitretin (RO 10-1670) and its metabolite (Ro 13-7652) after chronic administration. Dermatologica 1988;177:244–6.PubMedGoogle Scholar
  20. 20.
    Gollnick H, Bauer R, Brindley C, Orfanos CE, Plewig G, Wokalek H, Hoting E. Acitretin versus etretinate in psoriasis. J Am Acad Dermatol 1988;19:458–69.PubMedGoogle Scholar
  21. 21.
    Lambert WE, De Leenheer AP, De Bersaques JP, Kint A. Persistent etretinate levels in plasma after changing the therapy to acitretin. Arch Dermatol Res 1990;282(5):343–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Wiegand UW, Jensen BK. Pharmacokinetics of acitretin in humans. In: Saurat JH, ed. Retinoids: 10 years on. Basle: Karger, 1991:192–203.Google Scholar
  23. 23.
    Ito Y, Zile M, DeLuca HF, Ahrens HM. Metabolism of retinoic acid in vitamin A-deficient rats. Biochim Biophys Acta 1974;369:338–50.Google Scholar
  24. 24.
    Silva DP Jr., DeLuca HF. Metabolism of retinoic acidin vivo in the vitamin A-deficient rat. Biochem J 1982;206:33–41.PubMedGoogle Scholar
  25. 25.
    Frolik CA, Dart LL, Sporin MB. Metabolism of alltrans-retinyl acetate to retinoic acid in hamster tracheal organ culture. Biochim Biophys Acta 1981;663:329–35.PubMedGoogle Scholar
  26. 26.
    Yost RW, Harrison EH, Ross C. Esterification by rat liver microsomes of retinol found to cellular retinolbinding protein. J Biol Chem 1988;263:18693–701.PubMedGoogle Scholar
  27. 27.
    Barua AB, Olson JA. Chemical synthesis of all-trans-[11-3H]retinoylβ-glucuronide and its metabolism in ratsin vivo. Biochem J 1989;263:403–9.PubMedGoogle Scholar
  28. 28.
    Dunagin PE, Zachman RD, Olson JA. The identification of metabolites of retinal and retinoic acid in rat bile. Biochim Biophys Acta 1966;124:71–85.PubMedGoogle Scholar
  29. 29.
    Miller DA, DeLuca HF. Activation of retinoic acid by coenzyme A for the formation of ethyl retinoate. Proc Natl Acad Sci USA 1985;82:6419–22.PubMedGoogle Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1992

Authors and Affiliations

  • M. L. Bouvy
    • 1
  • M. C. J. M. Sturkenboom
    • 1
  • M. C. Cornel
    • 2
  • L. T. W. De Jong-Van den Berg
    • 1
  • B. H. C. Stricker
    • 3
  • H. Wesseling
    • 4
  1. 1.Department of Pharmacology and Pharmacotherapeutics, Section Social PharmacyUniversity Centre for PharmacyAW Groningenthe Netherlands
  2. 2.EUROCAT - Registration of congenital anomalies, Department of Medical GeneticsUniversity of GroningenAW Groningenthe Netherlands
  3. 3.Netherlands Centre for Monitoring of Adverse Reactions to DrugsHK Rijswijkthe Netherlands
  4. 4.Department of Clinical PharmacologyUniversity of Groningenthe Netherlands

Personalised recommendations