Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule?
Photosafety assessments are recommended for all new drug candidates intended for clinical use. In 2002, Testing guidances were issued by the regulatory authorities in the USA (2003) and Europe (2002). A key requirement is to measure the absorption of UV-visible light by a compound in the 290-700 nm range and to assess photostability. Further photosafety evaluation is recommended for molecules which absorb light energy in this region and may be unstable in light. Consequently, the current guidances do not specify what constitutes a significant level of light absorbance or photoinstability. The current study was undertaken to determine the level of light absorption by measuring the molar extinction coefficients (MEC) of a wide range of compounds reported in the literature to have known photosafety issues in humans. The results have shown that all compounds tested have absorbance intensities significantly above an MEC threshold of 1000 L mol(-1)cm(-1) and also display a wide range of photoinstability. The measurement of light absorption is a contributing part of an overall pre-clinical photosafety risk assessment process, whereas photostability assessments have proven to have limited value. Molecules with an MEC less than 1000 L mol(-1)cm(-1)are deemed less of a photosafety risk since this low level of light absorption is unlikely to prove harmful.
Henry
Brian
B
Pharmaceutical Sciences, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, UK. brian.henry@pfizer.com
Foti
Christopher
C
Alsante
Karen
K
D000042:Absorption; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D006801:Humans; D008027:Light; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000528:radiation effects*; D018570:Risk Assessment; D013056:Spectrophotometry, Ultraviolet; D018675:Toxicity Tests / Q000379:methods*
D004364:Pharmaceutical Preparations