Retinoids

Advances in Basic Research and Therapy

  • C. E. Orfanos
  • O. Braun-Falco
  • E. M. Farber
  • Ch. Grupper
  • M. K. Polano
  • R. Schuppli

Table of contents

  1. Front Matter
    Pages N1-XX
  2. Introduction

    1. C. E. Orfanos
      Pages 1-2
  3. Pharmacology and Toxicology of Retinoids

  4. Biological Effects of Retinoids

    1. Front Matter
      Pages 71-71
    2. R. Marks, A. Finlay, S. Nicholls, S. Barton
      Pages 77-83
    3. Ch. N. Ellis, R. C. Gold, R. C. Grekin, N. A. Swanson, Th. F. Anderson, J. J. Voorhees
      Pages 93-98
    4. A. Vahlquist, G. Michaëlsson, A. Kober, I. Sjöholm, G. Palmskog, U. Pettersson
      Pages 109-116

About these proceedings

Introduction

With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre­ sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19 different bio­ transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2.

Keywords

Hautkrankheit Retinsäure cancer skin disease therapy

Editors and affiliations

  • C. E. Orfanos
    • 1
  • O. Braun-Falco
    • 2
  • E. M. Farber
    • 3
  • Ch. Grupper
    • 4
  • M. K. Polano
    • 5
  • R. Schuppli
    • 6
  1. 1.Department of Dermatology, University Medical Center SteglitzThe Free University of BerlinBerlin 45West Germany
  2. 2.Universitäts-HautklinikMünchen 2West Germany
  3. 3.Department of DermatologyStanford University School of MedicineStanfordUSA
  4. 4.ParisFrance
  5. 5.Postdam 7, WarmondNetherlands
  6. 6.Dermatologische Universitätsklinik, Kantonsspital BaselBaselSwitzerland

Bibliographic information

  • DOI https://doi.org/10.1007/978-3-642-68023-6
  • Copyright Information Springer-Verlag Berlin Heidelberg 1981
  • Publisher Name Springer, Berlin, Heidelberg
  • eBook Packages Springer Book Archive
  • Print ISBN 978-3-642-68025-0
  • Online ISBN 978-3-642-68023-6
  • About this book