PMID- 24519524
OWN - NLM
STAT- MEDLINE
DCOM- 20141228
LR  - 20140421
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 139
IP  - 1
DP  - 2014 May
TI  - Integrated preclinical photosafety testing strategy for systemically applied 
      pharmaceuticals.
PG  - 245-56
LID - 10.1093/toxsci/kfu026 [doi]
AB  - Phototoxic properties of systemically applied pharmaceuticals may be the cause of 
      serious adverse drug reactions. Therefore, a reliable preclinical photosafety 
      assessment strategy, combining in vitro and in vivo approaches in a quantitative 
      manner, is important and has not been described so far. Here, we report the 
      establishment of an optimized modified murine local lymph node assay (LLNA), 
      adapted for phototoxicity assessment of systemically applied compounds, as well 
      as the test results for 34 drug candidates in this in vivo photo-LLNA. The drug 
      candidates were selected based on their ability to absorb ultraviolet/visible 
      light and the photo irritation factors (PIFs) determined in the well-established 
      in vitro 3T3 neutral red uptake phototoxicity test. An in vivo phototoxic 
      potential was identified for 13 of these drug candidates. The use of multiple 
      dose levels in the described murine in vivo phototoxicity studies enabled the 
      establishment of no- and/or lowest-observed-adverse-effect levels 
      (NOAELs/LOAELs), also supporting human photosafety assessment. An in vitro-in 
      vivo correlation demonstrated that a drug candidate classified as "phototoxic" in 
      vitro is not necessarily phototoxic in vivo. However, the probability for a drug 
      candidate to cause phototoxicity in vivo clearly correlated with the magnitude of 
      the phototoxicity identified in vitro.
FAU - Schumann, Jens
AU  - Schumann J
AD  - Novartis Institutes for BioMedical Research, Preclinical Safety, 4002 Basel, 
      Switzerland.
FAU - Boudon, Stephanie
AU  - Boudon S
FAU - Ulrich, Peter
AU  - Ulrich P
FAU - Loll, Nathalie
AU  - Loll N
FAU - Garcia, Deborah
AU  - Garcia D
FAU - Schaffner, Rene
AU  - Schaffner R
FAU - Streich, Jeannine
AU  - Streich J
FAU - Kittel, Birgit
AU  - Kittel B
FAU - Bauer, Daniel
AU  - Bauer D
LA  - eng
PT  - Journal Article
DEP - 20140211
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
SB  - IM
MH  - Animals
MH  - *Dermatitis, Phototoxic
MH  - Drug Evaluation, Preclinical
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Lymph Nodes/drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Spectrophotometry, Ultraviolet
MH  - Toxicity Tests/*methods
OTO - NOTNLM
OT  - local lymph node assay
OT  - photoirritation factor
OT  - photosafety
OT  - phototoxicity
EDAT- 2014/02/13 06:00
MHDA- 2014/12/30 06:00
CRDT- 2014/02/13 06:00
PHST- 2014/02/13 06:00 [entrez]
PHST- 2014/02/13 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - kfu026 [pii]
AID - 10.1093/toxsci/kfu026 [doi]
PST - ppublish
SO  - Toxicol Sci. 2014 May;139(1):245-56. doi: 10.1093/toxsci/kfu026. Epub 2014 Feb 
      11.