Dosage variability of veterinary drug products, containing furosemide, linked to tablet splitting

Furosemide is a potent diuretic drug widely used to treat congestive heart failure in dogs and cats, but it shows remarkable variability in bioavailability and efficacy when administered orally. In particular, a different diuretic effect can be detected after repeated administrations of the same medicinal product in the same animal. For this reason, we investigate the possible reasons for this peculiar behavior. Drug products for veterinary andhuman use are compared in terms of variability for tablet splitting, in vitro dissolution profiles (in different fluids that could simulate the gastrointestinal environment of pets), and drug distribution uniformity.

To study the in vitro performances of drug products in terms of variability.

Five veterinary products and five products for human use, containing different furosemide doses, are characterized. Tablets splitting uniformity, in vitro dissolution profiles in different fluids that could simulate the gastrointestinal environment of the different species, and drug content distribution, were tested.

The in vitro dissolution profiles of the different medicines are comparable but confirm a different dissolution rate as a function of the medium pH and volume. Many of the products considered show wide variability in the division performances of the scored tablets, and this problem could lead to the detected fluctuations in the diuretic effect. The four-leaf clover shape of a veterinary product appears to give rise to more uniform fractions. A uniform distribution of the drug in the tablets and their fractions is confirmed for all the products considered.

The possibility of tablets splitting allows considerable dosage flexibility, but a non-uniform break of the tablets to obtain the dosage suitable for the pet's weight, can cause dangerous over-or sub-dosing condition, especially in critical pathologies and in small breed pets.