PMID- 18958666
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20091216
LR  - 20081029
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 2
IP  - 3
DP  - 2005 Jul 1
TI  - Lack of respiratory and contact sensitizing potential of the intranasal antiviral 
      drug candidate rupintrivir (AG7088): a weight-of-the-evidence evaluation.
PG  - 123-39
LID - 10.1080/15476910500203925 [doi]
AB  - Rupintrivir, also known as AG7088, is a small molecule 3C protease inhibitor 
      designed to target human rhinovirus as a potential intranasal treatment for the 
      common cold. The ability of rupintrivir to induce both respiratory and contact 
      hypersensitivity responses was evaluated using a weight of the evidence approach. 
      A local lymph node assay (LLNA) in mice evaluating concentrations of rupintrivir 
      up to 50% in dimethylformamide showed no evidence of sensitizing capability. An 
      irritation study conducted in rabbits was performed to assess potential dermal 
      irritancy and provide information for worker safety guidelines. The study showed 
      no evidence of skin irritation when the material was placed in direct contact 
      with the skin in a semi-occluded fashion for four days. Quantitative whole body 
      autoradiography (QWBA) following intranasal instillation of the compound into 
      rabbits showed that the compound was retained in the nasal cavity or was 
      swallowed. No radioactivity was observed in the pulmonary regions of these 
      animals. Histopathologic evaluation of the nasopharyngeal tract and the lungs of 
      both rats and dogs exposed by intranasal instillation acutely or following 
      repeated intranasal exposures for 14 (rat) or 28 days (rat and dog) did not 
      reveal any evidence of irritation or inflammation in these regions of the 
      respiratory tract. These data demonstrate that rupintrivir does not cause 
      irritation or inflammatory responses that may precede the development of 
      sensitization of the skin or respiratory tract. It was concluded that the weight 
      of the available toxicologic evidence indicated that rupintrivir was not likely 
      to cause sensitization of either the skin or the respiratory tract in humans 
      following intranasal delivery.
FAU - Burns-Naas, Leigh Ann
AU  - Burns-Naas LA
AD  - Worldwide Safety Sciences, Pfizer Global Research and Development, San Diego, CA 
      92064, USA. leighann.burns@pfizer.com
FAU - Lee, Caroline
AU  - Lee C
FAU - Evering, Winston
AU  - Evering W
FAU - Ahern, Lisa
AU  - Ahern L
FAU - Webber, Stephanie
AU  - Webber S
FAU - Zorbas, Mark
AU  - Zorbas M
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
EDAT- 2008/10/30 09:00
MHDA- 2008/10/30 09:01
CRDT- 2008/10/30 09:00
PHST- 2008/10/30 09:00 [pubmed]
PHST- 2008/10/30 09:01 [medline]
PHST- 2008/10/30 09:00 [entrez]
AID - 725803189 [pii]
AID - 10.1080/15476910500203925 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2005 Jul 1;2(3):123-39. doi: 10.1080/15476910500203925.