title: Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF-200 aminolaevulinic acid declines with age.
abstract: BACKGROUND
  Topical photodynamic therapy (PDT) is a popular treatment modality in dermatology. The effect of PDT in epidermal cells depends on formation of protoporphyrin IX (PpIX) from 5-aminolevulinic acid (ALA). A variety of physiological changes in epidermal function occur with increasing age, but no studies have investigated whether PpIX formation is age-related.
  
  
  OBJECTIVE
  To investigate a possible relationship between age and PpIX formation.
  
  
  METHODS
  Methyl aminolaevulinate cream (MAL) and 5-ALA gel (BF-200 ALA) were applied to two identical fields on the forearm of 30 healthy volunteers for 24 h. The volunteers were divided into two age groups: a young group under 55 years (range 18-54) and an older group over 55 years (range 65-85). PpIX formation was measured noninvasively every hour from 1-5 h, and after 18, 21 and 24 h. Skin phototype, stratum corneum hydration and ultraviolet (UV) damage were also assessed. Treatment efficacy in relation to age was evaluated in 100 basal cell carcinomas (BCCs) treated with MAL-PDT.
  
  
  RESULTS
  Both photosensitizers induced significantly more PpIX formation in the younger group. Linear regression revealed a significant age-related decline in PpIX formation after the standard application time of 3 h (P < 0.001 for both treatments). Skin phototype, stratum corneum hydration and UV damage were not associated with PpIX formation. The treatment efficacy of BCCs 3 months after MAL-PDT was higher in young patients (P =  0.012).
  
  
  CONCLUSIONS
  PpIX formation in human skin declines with age. No explanation could be attributed to skin phototype, stratum corneum hydration or UV damage. The consequence might be reduced efficacy of PDT in the elderly.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400, Copenhagen NV, Denmark.
authors.forename: C V
authors.initials: CV
authors.lastname: Nissen
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400, Copenhagen NV, Denmark.
authors.forename: P A
authors.initials: PA
authors.lastname: Philipsen
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400, Copenhagen NV, Denmark.
authors.forename: H C
authors.initials: HC
authors.lastname: Wulf
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D005453:Fluorescence; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011524:Protoporphyrins / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX