Magnetic Marker Monitoring of Furosemide-containing Gastroretentive Formulation in Healthy Male Subjects (Fasting and Fed Conditions)
Condition: Gastroretentive Drug Formulation of Furosemide; Oedema
MeSH terms: Edema
Study type: Interventional
Phase: Phase 1

Summary: 
      Furosemide is a diuretic drug, used in the treatment of oedematous states associated with
      cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to
      thiazide diuretics. Furosemide is also used in the treatment of hypertension.

      Absorption of furosemide from the gastrointestinal tract is fairly rapid; bioavailability is
      60-70%, but variable and not predictable, with large intra- and inter-individual variability,
      and are influenced by dosage form, underlying diseases, and by the presence of food after
      oral administration. Data from animal model show that furosemide administered into the
      stomach is more rapidly absorbed than if is administered into the small intestine.

      To increase the residency of furosemide in the stomach after oral administration, a
      gastroretentive dosage form (GRDF) of furosemide has been developed. In the current study,
      the new formulation (30mg furosemide coated tablet) will be tested in healthy male subjects.
      Absorption will be characterised by an effective and safe imaging technique - Magnetic Marker
      Monitoring (MMM), based on Fe3O4 added to the drug product to generate magnetic signal that
      can be used for up to 12 h after furosemide administration to localize the medication in the
      gastrointestinal tract. Fe3O4 is frequently used as colouring pigment in medicinal products.
      It does not exhibit own pharmacodynamic activity and is considered as an inactive ingredient.

      In the current study, GRDF formulation of furosemide will be evaluated for: gastric residence
      as well as pharmacokinetic and pharmacodynamic characteristics under fasting and fed
      conditions. As part of the study, the subjects will be hospitalized for 1 day during each
      drug administration. The duration of the stay will depend on the intestinal behaviour of the
      investigational product.
    

Detailed description: 
      Furosemide is a diuretic drug, widely used in the treatment of oedematous states associated
      with cardiac, renal, and hepatic disorder, and may be effective in patients unresponsive to
      thiazide diuretics. Furosemide is also used in the treatment of hypertension.

      Absorption of furosemide from the gastrointestinal tract is fairly rapid. Bioavailability is
      reported as 60-70%, but is variable and not predictable. The rate and extent of absorption
      show a large intra- and inter-individual variability and are influenced by dosage form,
      underlying diseases, and by the presence of food after oral administration. Results obtained
      with an animal model indicate that furosemide administered into the stomach is more rapidly
      absorbed than if is is administered into the small intestine.

      To increase the residency of furosemide in the stomach after oral administration, a
      gastroretentive dosage form (GRDF) of furosemide has been developed. In this study, the new
      formulation(30mg furosemide coated tablet) will be tested in healthy male subjects.
      Absorption will be characterised by imaging technique - Magnetic Marker Monitoring (MMM),
      which is the most effective and safe imaging technique currently available. MMM is based on a
      iron-III-oxide (Fe3O4) added to the drug product to generate magnetic signal that can be used
      to localize the administered medication in the gastrointestinal tract.

      Fe3O4 is frequently used as colouring pigment in medicinal products. It does not exhibit own
      pharmacodynamic activity and thus, it is considered as clinically inactive ingredient. Fe3O4
      exhibits a dipole moment and thus, after magnetisation of solid oral dosage forms containing
      homogenously distributed Fe3O4, the product generates a magnetic signal, which can be used
      for localisation of the dosage form in the gastrointestinal tract by Magnetic Marker
      Monitoring technique.

      The aim of the current study is to evaluate the GRDF formulation of furosemide for: gastric
      residence, pharmacokinetic and pharmacodynamic characteristics under fasting and fed
      conditions. As part of the study, the subjects will be hospitalized for 1 day during each
      drug administration (i.e. a total of two days). The duration of the stay will depend on the
      intestinal behaviour of the investigational product. The MMM monitoring be performed for up
      to 12 h after furosemide administration. For pharmacokinetic determinations, liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS) will be used to analyze
      furosemide in plasma.
    

Intervention name(s): GRDF furosemide
Intervention type(s): Drug
Intervention description(s): The GRDF furosemide tablet contains Fe3O4, which serves as an inactive magnetic marker to allow monitoring of the tablet transit through the gastrointestinal tract, using the MMM imaging technique.
Other intervention name(s): GRDF furosemide is a gastro retentive dosage form of furesomide
Intervention MeSH terms: Furosemide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Gastroretentive drug formulation; Furosemide; Magnetic Marker Monitoring; Magnetic marker; Oedema