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Abstract
The present study was a summary of the current regulations and current investigation into the preclinical testing of systemic drug agents on phototoxicity. The aim was to investigate whether these test methods are sufficient to assess the reactions of such drugs under UV irradiation and if this is a basis for a secure phototherapy.
The first step was a systematic research of the question whether there are standardized preclinical testing procedures to detect the phototoxic potential of systemic pharmaceutical active compounds and to compare them.
It was clarified whether drugs can be tested at all efficiently and comparable to the current regulations.
In a further step a listing of systemic drug agents with phototoxic potential is based on data from the literature. As far as possible, the expected severity of phototoxic reactions was identified.
The criteria that led each substance to determine the phototoxic effects were taken into account. The action spectrum and the reaction maximum of the active substances were specified. The list is in Table 1. Supplementary more phototoxic substances are shown in Table 2.
In summary the following main results can be stated:
Phototoxicity is a dose-dependent non-immunological response to UV radiation and visible light, which is expressed as a sunburn-like skin reaction triggered by pharmaceutical and chemical substances.
In the field of test methods the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT) is currently the leading in vitro test. Additional in vitro methods are the Red Blood Cell Phototoxicity Test (RBC PT) and the Human 3-D Skin Model In Vitro Phototoxicity Test (H3D PT). Additional in vivo methods include the Photo Hen´s Egg Test (PHET), the Acute Phototoxicity Assay In Guinea Pigs and the Integrated Model For The Differentiation Of Chemical-Induced Allergic And Irritant Skin Reactions (IMDS). Although several test methods are used to complement each other, all response options cannot be recovered by the in vitro and in vivo methods. Therefore it is difficult to exclude an unexpected phototoxic reaction in advance. For this reason clinical trials are still necessary.
Among the numerous guidelines the only mandatory regulations for phototoxicity testing are the German Drug Law and the eu directive 86 609 eec. These regulations constitute orienting framework, which have to be substantiated by further specifications of the American (FDA) and European (EMEA) Drug Administration, and the Declaration of Helsinki (ICH-Guideline). However, the Guidance for Industry (FDA), the Note For Guidance on Photosafety Testing (EMEA) and the regulation for Good Clinical Practice (ICH-Guideline) are only guidelines and should not be strictly followed. It follows that the legislation as a basis for clear guidelines regarding photosafety testing and phototherapy is still insufficient.
For a safer phototherapy it is recommended the introduction of mandatory international standards regarding preclinical and clinical testing methods to detect the phototoxic potential of medicinal drugs. At the current state of policy the systematic compilation of previously known phototoxic substances (Tables 1 and 2 in the Appendix) and the concept to prevent serious phototoxic reactions by the UV treatment (page 59) make it easier to classify and to reduce the risk of phototoxic reactions during phototherapy.
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Dates
Created: 2014Issued: 2014-12-16
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
photosensitivityphototoxic reactionsphototoxicityLichttoxizitätphototoxische Reaktion
DFG-subjects
Phototoxizität
DDC-Numbers
610
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Menzel, Henrik (1064146597): Über Phototoxizität Klinik-Richtlinien-Testmethoden. : Philipps-Universität Marburg 2014-12-16. DOI: https://doi.org/10.17192/z2014.0476.
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This item has been published with the following license: In Copyright