title: Safety studies of topical imiquimod 5% cream on normal skin exposed to ultraviolet radiation.
abstract: BACKGROUND
  Imiquimod 5% topical cream is an immune response modifier that induces interferon alpha and interleukin-12, and exhibits antiviral and tumor-inhibiting properties. It is currently available for treatment of genital and perianal warts. Three randomized, open-label or assessor-blinded, placebo-controlled studies were carried out to assess its safety on normal white skin exposed to ultraviolet radiation (UVR).
  
  
  METHODS
  Healthy white volunteer adult subjects between the ages of 18 and 60 years with skin types I, II or III (Fitzpatrick Scale, US Federal Register 43:38260, 1978) were invited to participate. Imiquimod 5% cream (each dose approximately 0.1-0.2 ml) was compared with placebo cream. Two preliminary studies assessed the potential photosensitizing properties of the drug, and the third study added measurement of sunburn cell counts (SBC) and deoxyribonucleic acid (DNA) pyrimidine dimer (PD) formation. The three studies were: a 6-week standard photocontact allergenicity bioassay; a 4-day standard phototoxicity bioassay; and a 4-week photodamage study using biopsy sample analyses to determine SBC or PD frequency.
  
  
  RESULTS
  Imiquimod had no detectable potential for inducing either photocontact allergy (n=115) or phototoxicity (n=20). The final study further assessing photodamage potential of imiquimod included 44 subjects. There were no significant differences between imiquimod vs. the control (no drug+UVB) for SBC counts (mean 0.88 vs. 0.93), or PD frequency (mean 60.86 vs. 70.03).
  
  
  CONCLUSIONS
  Results from the two preliminary safety studies suggest that imiquimod 5% cream does not possess a detectable photosensitizing potential in humans. Furthermore, topical imiquimod did not enhance UVR-induced damage to epidermal cells or DNA.
authors.affiliation: KGL, Inc. (Ivy Laboratories), University City Science Center, 3401 Market Street, Suite 226 and Suite 232, Philadelphia, PA 19104-3355, USA. marijane@bellatlantic.net
authors.forename: Kays
authors.initials: K
authors.lastname: Kaidbey
authors.forename: Mary
authors.initials: M
authors.lastname: Owens
authors.forename: Margo
authors.initials: M
authors.lastname: Liberda
authors.forename: Michael
authors.initials: M
authors.lastname: Smith
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002452:Cell Count; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D017454:Dermatitis, Photoallergic / Q000473:pathology; D017484:Dermatitis, Phototoxic; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007369:Interferon Inducers / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D013471:Sunburn / Q000473:pathology; D014466:Ultraviolet Rays
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D007369:Interferon Inducers; D011743:Pyrimidines; D004247:DNA; D000077271:Imiquimod