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Administering a diuretic-furosemide-to cats

Nov 30, 2018

November 30, 2018

Pharmacokinetics of furosemide after intravenous, oral and transdermal administration to cats

Sleeper MM, O'Donnell P, Fitzgerald C, Papich MG. Pharmacokinetics of furosemide after intravenous, oral and transdermal administration to cats. J Feline Med Surg. 2018 Oct 19. 

The mainstay of therapy for congestive heart failure (CHF) in cats remains furosemide. It is used intravenously or intramuscularly in cases of acute heart failure (or of acute decompensation) and chronically by an oral route. It is by far the most commonly used diuretic in veterinary medicine, and is one of the few drugs that are widely agreed upon to extend the duration and quality of life in cats with CHF. It is generally administered one to several times a day for the remainder of a cat’s life after diagnosis of CHF.

In many feline patients, oral medication is difficult or impossible to administer. This is especially true of cats with CHF, where normally tolerable stressors may exacerbate disease. Several drugs have successfully been administered to cats via a transdermal route through the pinna of the ear. This route of administration may allow easier and less stressful therapy for the cat and the owner, however many drugs have little to no systemic absorption or cause adverse cutaneous reactions.

The purpose of this study was to determine the systemic bioavailability of transdermally applied furosemide in cats. The study was designed as a prospective crossover trial involving 6 healthy adult cats receiving intravenous, oral, and transdermal furosemide. Three-week washouts were performed between each crossover. The transdermal drug was compounded into a lipoderm base (a commonly used commercial vehicle for transdermal drug application) and used within 7 days of compounding.

Cats were administered furosemide at a dose of 2mg/kg. Drug was administered once for the oral and intravenous routes, and every 12 hours for 3 days for the transdermal route (to determine if chronic dosing allowed a higher bioavailability).  Ears were alternated morning and night during the three-day period.

For the oral and intravenous (IV) phases, blood was collected from a catheter at 0.5, 1, 2, 3, 4, 6,and 8h post administration. For the transdermal phase, blood was collected at 1, 2, 3, 4, 6, and 72h post administration. Plasma furosemide levels were measured using reversed phase high pressure liquid chromatography.

Both oral and IV furosemide concentrations declined rapidly after administration, with a mean half-life of 2.25h IV and 1.2h orally. Volume of distribution was equivalent to extracellular water volume, and clearance was comparable to published creatinine clearance, indicating a solely renal excretion.

Plasma levels after TD administration remained either very low or undetectable over the course of the study. Maximal concentrations reached 0.13ug/mL. This compares to peak concentrations of 12ug/mL IV and 2.5ug/mL orally. This concentration is sub-therapeutic, and was only detected after multiple administrations.

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Excerpt from paper. Plasma concentration of furosemide by time. TD route not shown as values are near zero

Potency of the compounded drug was measured at 3 and 7 days after production and was found to range from 97% to 102%, within acceptable margins of error.

Despite the fact that chemically, furosemide has many criteria that make it appear a good choice for TD administration (small molecular size, low melting point, low daily dose, etc), it appears to be ineffective when applied by this route.

The authors conclude that transdermal furosemide is unlikely to be effective in cats, as it is not absorbed to any significant extent. As such, its use should be avoided. (MRK)

See Also

Gordon SG and Cote E. Pharmacotherapy of feline cardiomyopathy: chronic management of heart failure. J Vet Cardiol 2015; 17: S159–S172

MacGregor JM, Rush JE, Rozanski EA, et al. Comparison of pharmacodynamic variables following oral versus transdermal administration of atenolol to healthy cats. Am J Vet Res 2008; 69: 39–44.

Choy YB and Prausnitz MR. The rule of five for non-oral routes of drug delivery: ophthalmic, inhalation and transdermal. Pharm Res 2011; 28: 943–948.

Cardiac disease Congestive heart failure Diuretic

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