Standardized UV vis spectra as the foundation for a threshold-based, integrated photosafety evaluation

被引：17

作者：

Bauer, Daniel ^{[1
]}

Averett, Lacey A. ^{[2
]}

De Smedt, Ann ^{[3
]}

Kleinman, Mark H. ^{[4
]}

Muster, Wolfgang ^{[5
]}

Pettersen, Betty A. ^{[6
]}

Robles, Catherine ^{[7
]}

机构：

[1] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland

[2] GlaxoSmithKline, GSK, Platform Technol & Sci, King Of Prussia, PA 19406 USA

[3] Janssen Res & Dev, Beerse, Belgium

[4] GlaxoSmithKline, GSK, Projects Clin Platform & Sci, King Of Prussia, PA 19406 USA

[5] Hoffmann La Roche AG, Nonclin Drug Safety, CH-4070 Basel, Switzerland

[6] Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA

[7] Sanofi R&D, Montpellier, France

来源：

REGULATORY TOXICOLOGY AND PHARMACOLOGY | 2014年 / 68卷 / 01期

关键词：

Photosafety; Phototoxicity; Photoreactivity; Molar extinction coefficient; Molar absorptivity; Threshold; Sunlight; Irradiation; PHOTOTOXICITY; PHOTOSENSITIVITY;

D O I：

10.1016/j.yrtph.2013.11.007

中图分类号：

DF [法律]; D9 [法律]; R [医药、卫生];

学科分类号：

030101 [法学理论]; 030111 [法律史学]; 100218 [急诊医学];

摘要：

Phototoxicity is a relatively common phenomenon and is an adverse effect of some systemic drugs. The fundamental initial step of photochemical reactivity is absorption of a photon; however, little guidance has been provided thus far regarding how ultraviolet-visible (UV-vis) light absorption spectra may be used to inform testing strategies for investigational drugs. Here we report the results of an inter-laboratory study comparing the data from harmonized UV-vis light absorption spectra obtained in methanol with data from the in vitro 3T3 Neutral Red Uptake Phototoxicity Test. Six pharmaceutical companies submitted data according to predefined quality criteria for 76 compounds covering a wide range of chemical classes showing a diverse but "positive-enhanced distribution of photo irritation factors (22%: PIF <2, 12%: PIF 2-5, 66%; PIF > 5). For compounds being formally positive (PIF value above 5) the lowest reported molar extinction coefficient (MEC) was 1700 L mol(-1) cm(-1) in methanol. However, the majority of these formally positive compounds showed MEC values being significantly higher (up to almost 40,000 L mol(-1) cm(-1)). In conclusion, an MEC value of 1000 L mol(-1) cm(-1) may represent a reasonable and pragmatic threshold warranting further experimental photosafety evaluation. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：70 / 75

页数：6

共 17 条

[1]

[Anonymous], 2009, Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3

[2]

The 3T3 neutral red uptake phototoxicity test: Practical experience and implications for phototoxicity testing - The report of an ECVAM-EFPIA workshop [J].

Ceridono, Mara ;

Tellner, Paer ;

Bauer, Daniel ;

Barroso, Joao ;

Alepee, Nathalie ;

Corvi, Raffaella ;

De Smedt, Ann ;

Fellows, Mick D. ;

Gibbs, Neil K. ;

Heisler, Eckhard ;

Jacobs, Abigail ;

Jirova, Dagmar ;

Jones, David ;

Kandarova, Helena ;

Kasper, Peter ;

Akunda, Jacqueline Kinyamu ;

Krul, Cyrille ;

Learn, Douglas ;

Liebsch, Manfred ;

Lynch, Anthony M. ;

Muster, Wolfgang ;

Nakamura, Kazuichi ;

Nash, J. Frank ;

Pfannenbecker, Uwe ;

Phillips, Gareth ;

Robles, Catherine ;

Rogiers, Vera ;

De Water, Femke Van ;

Liminga, Ulla Wandel ;

Vohr, Hans-Werner ;

Wattrelos, Olivier ;

Woods, Julie ;

Zuang, Valerie ;

Kreysa, Joachim ;

Wilcox, Phil .

REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2012, 63 (03) :480-488

[3]

EMA, 2002, CPMPSWP39801 EMA

[4]

FDA Center for Drug Evaluation and Research(CDER), 2003, FDA GUID IND PHOT TE

[5]

Photosensitivity due to drugs [J].

Ferguson, J .

PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE, 2002, 18 (05) :262-269

[6]

Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule? [J].

Henry, Brian ;

Foti, Christopher ;

Alsante, Karen .

JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2009, 96 (01) :57-62

[7]

ICH S10, 2013, PHOT EV PHARM

[8]

Review of the performance of the 3T3 NRU in vitro phototoxicity assay in the pharmaceutical industry [J].

Lynch, Anthony M. ;

Wilcox, Phillip .

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, 2011, 63 (03) :209-214

[9]

Drug-induced cutaneous photosensitivity - Incidence, mechanism, prevention and management [J].

Moore, DE .

DRUG SAFETY, 2002, 25 (05) :345-372

[10]

OECD, 1981, UV VIS ABS SPECTR OE

← 1 2 →