Pharmacokinetics and bioavailability of furosemide in sheep

Abstract

The pharmacokinetics and bioavailability of furosemide were determined following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at 2.5 mg/kg dose in sheep. The study was conducted on six healthy sheep in a three‐way, three‐period, crossover pharmacokinetic design with a 15‐day washout period. In first period, furosemide was randomly administered via IV to 2 sheep, IM to 2 sheep and SC to 2 sheep. In second and third periods, each sheep received furosemide via different routes of administration with the 15‐day washout period. Plasma concentrations were determined using a high‐performance liquid chromatography assay and analyzed by noncompartmental method. The mean total clearance and volume of distribution at steady state following IV administration were 0.24 L h‐1 kg‐1 and 0.17 L/kg, respectively. The elimination half‐life was similar for all administration routes. The mean peak plasma concentrations of IM and SC administration were 10.33 and 3.18 μg/ml at 0.33 and 0.42 hr, respectively. The mean bioavailability of IM and SC administration was 97.91% and 37.98%, respectively. The IM injection of furosemide may be the alternative routes in addition to IV. However, further research is required to determine the effect of dose and route of administration on the clinical efficacy of furosemide in sheep.

Pharmacokinetics of furosemide in goats following intravenous, intramuscular, and subcutaneous administrations

“…The C max of furosemide after IM administration in goats was 11.19 (10.33–11.95) µg/ml, which was similar to that reported in sheep (10.33 ± 0.63 µg/ml, Durna Corum et al, 2020) and higher than dose‐normalized value (3.5 µg/ml at 2.5 mg/kg) in camels (Ali et al, 1998). The T max of IM route in goats was 0.23 (0.16–0.25) h, which was similar to that reported in camels (0.25 h, Ali et al, 1998) and sheep (0.33 h, Durna Corum et al, 2020). In goats, the C max of furosemide following SC administration was 6.49 (5.92–7.00) μg/ml, which was higher than that in sheep (3.18 ± 0.24 μg/ml, Durna Corum et al, 2020), but T max of SC route in goats (0.39 h) was similar to that in sheep (0.42 h, Durna Corum et al, 2020).…”

“…The t 1/2ʎz , V dss, and Cl T after IV administration of furosemide in goats were 0.71 (0.67–0.76) h, 0.17 (0.16–0.19) L/kg, and 0.30 (0.27–0.33) L/h/kg, respectively. These values were toward the lower start of the range of t 1/2ʎz (from 0.51 to 3.42 h), V d (from 0.17 h to 0.65 L/kg), and Cl T (from 0.15 to 0.9 L/h/kg) previously reported in other domestic species (Ali et al, 1998; Durna Corum et al, 2020; Dyke et al, 1996; Hirai et al, 1992; Johansson et al, 2004; Knych et al, 2018; Miceli et al, 1990; Miyazaki et al, 1990; Sleeper et al, 2019). In this study, the E body of furosemide for IV administration in goats was calculated as 0.056 (0.052–0.062), which exhibited a low extraction ratio of furosemide.…”

“…After the administration of furosemide via IV, IM, and SC routes in goats, the t 1/2ʎz was 0.71 (0.67–0.76), 0.69 (0.61–0.74), and 0.70 (0.67–0.79) h, respectively, and there was no significant difference between the routes of administration. The t 1/2ʎz of furosemide were similar for different administration routes in camels (IV; 1.96 h, IM; 1.82 h, Ali et al, 1998) and sheep (IV; 0.79 ± 0.04 h, IM; 0.80 ± 0.05 h, SC; 0.80 ± 0.02 h, Durna Corum et al, 2020). In this study, the MAT and MRT after SC administration were longer than those after IM administration.…”

“…In goats, the bioavailability of furosemide after SC administration was 70.80 (55.77–86.67)%, which was higher than that in sheep (38%, Durna Corum et al, 2020). In this study, the bioavailability of furosemide after IM administration was good with 109.84 (104.92–116.99)%.…”

“…In this study, the E body of furosemide for IV administration in goats was calculated as 0.056 (0.052–0.062), which exhibited a low extraction ratio of furosemide. The E body of furosemide would be classified as low in sheep (Durna Corum et al, 2020), camels (Ali et al, 1998), dogs (Hirai et al, 1992), and cat (Sleeper et al, 2019), because it is around 0.05, but medium in horses (Dyke et al, 1996; Johansson et al, 2004), because it is around 0.15 (Toutain & Bousquet‐Melou, 2004a). This may indicate that sheep, goats, camels, dogs, and cats have the same ability to eliminate furosemide (Toutain & Bousquet‐Melou, 2004a).…”