FDA Approves Optical Imaging Agent for Visualization of Malignant Tissue During Gliomas Surgery

FDA Approves Optical Imaging Agent for Visualization of Malignant Tissue During Gliomas Surgery

On June 6, 2017, the U.S. Food and Drug Administration (FDA) approved Gleolan [aminolevulinic acid hydrochloride (ALA HCl)] as an optical imaging agent indicated in patients with gliomas (suspected World Health Organization Grades III or IV on preoperative imaging) as an adjunct for the visualization of malignant tissue during surgery.

ChemSpider 2D Image | Aminolevulinic acid hydrochloride | C5H10ClNO3

The approved recommended reconstituted oral dose of Gleolan is 20 mg/kg administered 3 hours (range 2 to 4 hours) prior to induction of anesthesia. During neurosurgery, Gleolan is used with an operating microscope adapted with a blue emitting light source and filters for excitation light of wavelength 375 to 440 nm, and observation at wavelengths of 620 to 710 nm. Due to the risk of phototoxic reactions, do not administer phototoxic drugs for 24 hours during the perioperative period. Reduce exposure to sunlight or room lights for 24 hours postoperatively.

Mechanism of Action (MOA), General Pharmacokinetics (PK), and Pharmacodynamics (PD)

  • MOA: Exogenous administration of ALA HCl leads to accumulation of its metabolite protoporphyrin IX (PpIX) in tumor cells. Under an operating microscope adapted with a specific blue emitting light source and filters, tumor tissue is visualized as red fluorescence. Tissue lacking sufficient PpIX concentrations appears blue.
  • Absorption: The mean absolute bioavailability of ALA HCl following the approved recommended dose of Gleolan solution was 100%. Maximum ALA plasma concentrations were reached within a median of 0.8 hour. The Tmax for PpIX occurred within a median of 4 hours.
  • Protein Binding: The mean protein binding of ALA was 12% at concentrations up to approximately 25% of the maximal concentration following the approved recommended dose of Gleolan.
  • Half-Life: The mean half-life of ALA is approximately 1 hour. The mean elimination half-life of PpIX is 3.6 hours.
  • Metabolism: Exogenous ALA is metabolized to PpIX, but the fraction of administered ALA that is metabolized to PpIX is unknown. The average plasma AUC of PpIX is < 6% of that of ALA.
  • Excretion: The mean excretion of parent ALA in urine in the 12 hours following administration of the approved recommended dose of Gleolan was 34%.
by FDA
Source: https://www.pharmpro.com
June 14, 2017 / Pharma News