May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
The Prediction for Clinical Drug Interaction of Nipradilol by in vitro Enzyme Kinetic study
Author Affiliations & Notes
  • S. Shimada
    Pharmacology, Kowa, Higashimurayama, Japan
  • K. Mizuno
    Pharmacology, Kowa, Higashimurayama, Japan
  • T. Koide
    Pharmacology, Kowa, Higashimurayama, Japan
  • T. Ohshima
    Pharmacology, Kowa, Higashimurayama, Japan
  • J. Matsumoto
    Pharmacology, Kowa, Higashimurayama, Japan
  • Y. Hattori
    Pharmacology, Kowa, Higashimurayama, Japan
  • Footnotes
    Commercial Relationships  S. Shimada, Kowa Co., Ltd., E; K. Mizuno, Kowa Co., Ltd., E; T. Koide, Kowa Co., Ltd., E; T. Ohshima, Kowa Co., Ltd., E; J. Matsumoto, Kowa Co., Ltd., E; Y. Hattori, Kowa Co., Ltd., E.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 421. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S. Shimada, K. Mizuno, T. Koide, T. Ohshima, J. Matsumoto, Y. Hattori; The Prediction for Clinical Drug Interaction of Nipradilol by in vitro Enzyme Kinetic study . Invest. Ophthalmol. Vis. Sci. 2006;47(13):421.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : To predict the drug–drug interaction of nipradilol, which has ß–blocking property with NO donating action and is commercially available for the treatment of glaucoma in Japan, the metabolic characteristic was investigated using human tissue.

Methods: : [14C]nipradilol was reacted with cytochrome P450s (CYPs) and glutathione S–transferases (GSTs) which were drug metabolic enzymes in a fraction of human liver. Its metabolites were measured by Radio–HPLC assay and the kinetic parameters were calculated.

Results: : It was revealed that some metabolic enzymes metabolized nipradilol in the liver tissue. According to the kinetic parameters, the contribution rate of the metabolism was high due to denitration by GST, 4–hydroxylation by CYP2D6, deisopropylation by CYP1A2. The Km value for the metabolic reaction of nipradilol in the human microsome was from 11.9 to 22.2 µmol/L. In addition, there was no practical inhibition on the metabolic reaction via CYP1A2, 2C9, 2C19, and 3A4 (IC50>50 µmol/L). The IC50 for inhibition of CYP2D6 by nipradilol was 16.5 µmol/L, which was high enough in comparison with the plasma concentration of nipradilol (0.3 nmol/L) after the topical instillation at a clinical dose for the treatment of glaucoma.

Conclusions: : These results indicate that nipradilol hardly causes a drug–drug interaction by concomitant administration and that genetic polymorphism will not affect the nipradilol metabolism in the clinical use for the treatment of glaucoma.

Keywords: metabolism • drug toxicity/drug effects • enzymes/enzyme inhibitors 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.