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.
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.