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

Abstract

Objectives The aim of this study was to determine the pharmacokinetics of furosemide in cats following intravenous (IV), oral and transdermal administration. Methods This study used six healthy adult cats in a three-phase design to compare plasma furosemide concentrations in cats that received one IV 2 mg/kg dose of furosemide, one oral 2 mg/kg dose of furosemide and 3 days of q12h dosing with 2 mg/kg furosemide transdermally applied to the ear pinna. Results After IV administration the elimination half-life was (mean and coefficient of variation) 2.25 h (72%), systemic clearance was 149 ml/kg/h (27.4%) and volume of distribution was 227 ml/kg (22%). After oral administration the terminal half-life was 1.2 h (18.7%), peak concentration was 3.4 μg/ml (51.7%) and bioavailability was 48.4%. The transdermal plasma concentrations were undetectable or very low at most time points, and pharmacokinetics were not determined from the transdermal dose. Conclusions and relevance Furosemide was rapidly eliminated in cats after oral and IV administration and is probably best administered orally at least q12h in cats with heart failure. The oral dose absorbed was approximately 50%, but the absorption from transdermal administration was negligible.

Pharmacokinetics and bioavailability of furosemide in sheep

“…In addition, furosemide has been reported to treat edema in heartwater (cowdriosis) (Shakespeare et al., 1998) and to reverse tissue hypoxia in septic acute kidney injury (Iguchi et al., 2019) and to prevent postoperative pulmonary edema in cardiovascular surgeries in sheep (DiVincenti et al., 2014). The pharmacokinetics of furosemide was determined in horses (Dyke et al., 1996; Johansson et al., 2004), dog (Hirai et al., 1992), camel (Ali et al., 1998), piglets (Miceli et al., 1990), and cats (Sleeper et al., 2019). The studies have shown apparent differences in the effects and pharmacokinetics of furosemide for different routes of the administration among species (Ali et al., 1998; Johansson et al., 2004; Sleeper et al., 2019).…”

“…The pharmacokinetics of furosemide was determined in horses (Dyke et al., 1996; Johansson et al., 2004), dog (Hirai et al., 1992), camel (Ali et al., 1998), piglets (Miceli et al., 1990), and cats (Sleeper et al., 2019). The studies have shown apparent differences in the effects and pharmacokinetics of furosemide for different routes of the administration among species (Ali et al., 1998; Johansson et al., 2004; Sleeper et al., 2019). We hypothesized that intramuscular (IM) and subcutaneous (SC) injections of furosemide would be used as an alternative route in sheep by the reach to similar total exposure (area under the curve) comparable to those achieved by intravenous (IV) administration.…”

Pharmacokinetics and Diuretic Effect of Furosemide after Single Intravenous, Oral Tablet, and Newly Developed Oral Disintegrating Film Administration in Healthy Beagle Dogs

“…In the body, furosemide moves across the renal tubule from the plasma to the lumen of the nephron; thus, furosemide acting on henle's loop of renal tubule should have a short duration of effects if its half-life is short (7). After IV administration, the C max was slightly higher than that after OUT or FS-ODF administration, whereas the T 1/2 and T max were slightly lower.…”

“…It is used in animals for the treatment of pulmonary edema, udder edema, hypercalciuric nephropathy, uremia, and hypertension. Additionally, it reduces the incidence of sterile hemorrhagic cystitis associated with cyclophosphamide administration in dogs and is used as adjunctive therapy in hyperkalemia (2)(3)(4)(5)(6)(7)(8)(9)(10). The PK/PD properties of loop diuretics, including furosemide after IV and PO administration, have been well investigated in both human and veterinary medicine (5,8,(11)(12)(13)(14).…”

“…The study on furosemide administration using sublingual bioadhesive lm showed ex vivo mucoadhesion using the buccal mucosa and permeability using the tongue excised from slaughtered pigs (24). And the alternative route of administration of furosemide have not been reported except for a study that the therapeutic effect of the transdermal application of furosemide to cats is negligible compared to that after oral and IV administration (7). However, there are no announced studies on alternative administration routes in dogs.…”