Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Hori, Yuichi; Ohshima, Naoko; Kanai, Kazuaki; Hoshi, Fumio; Itoh, Naoyuki; Higuchi, Seiichi

doi:10.1292/jvms.09-0259

Cited by 14 publications

(19 citation statements)

References 33 publications

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“…Torasemide-inducted diuresis was comparable to a previous study (16), where dogs were administered 0.2 mg/kg torasemide twice a day (60 and 90 mL/kg/day after day 1 and 14, respectively). In the present study, diuresis after 10 treatment days were higher than after a single treatment day for high doses torasemide (≥0.3 mg/kg/day), whereas for doses up to 0.2 mg/kg/day, the daily diuresis remained constant over time.…”

Section: Pk and Pd Of Torasemidesupporting

confidence: 82%

Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs

et al. 2020

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Torasemide is a loop diuretic licensed in dogs for cardiogenic pulmonary oedema. The aim of this pharmacokinetic-pharmacodynamic (PK/PD) study was to define an optimally effective dosage regimen based on preclinical data. In a first study, 5 dogs received once-daily oral torasemide (0, 0.1, 0.2, 0.4, 0.8 mg/kg/day) for 14 days. A second study compared once-daily oral torasemide (0, 0.1, 0.2, 0.3, 0.4 mg/kg/day) to twice-daily furosemide (1, 2, 4, 8 mg/kg/day). For all doses of the second study, 11 dogs received a first day of treatment, followed by a 3 day washout and resumed daily treatment for 10 days (until Day 14). Blood and urine were collected to measure urinary torasemide excretion and plasma torasemide concentrations and daily diuresis and natriuresis. Torasemide PK was linear. After rapid absorption (T max 0.5-1 h), 61% of the bioavailable torasemide was eliminated unchanged in urine. Diuresis and natriuresis observed with torasemide were similar to the ones obtained after furosemide (daily dose-ratios: 1/20 to 1/10). The average diuresis increased from baseline (220 ± 53 mL/day for 10 kg dogs) to 730 ±120 mL after the first torasemide administration and up to 1150 ± 252 mL after 10 administrations at the highest dose. At higher doses (≥0.3 mg/kg/day), daily diureses after 10 diuretic treatment-days were higher than Day 1 and variable between dogs; in contrast, diureses remained constant over time and less variable for doses up to 0.2 mg/kg/day. Natriuresis peaked after the first day and decreased dramatically after the 2nd treatment-day then stabilized to a value close to baseline, except for 0.4 mg/kg/day. Urinary torasemide excretion predicted pharmacodynamics better than plasma concentrations. The decrease in natriuresis observed was successfully modeled using a resistance mechanism; this is likely due to a reabsorption of sodium which did not seem however to affect the volume of urine excreted. For a daily target diuresis of 460 mL/dog/day in severe pulmonary oedema (net fluid loss 240 mL/dog/day), a computed dose of 0.26 mg/kg/day (3.5 mg/kg/day furosemide-equivalent) was selected for clinical studies. Due to high inter-individual variability in diureses at doses ≥0.3 mg/kg, higher doses should be limited to 3-5 days to avoid supra-clinical effects in high responders.

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Section: Pk and Pd Of Torasemidesupporting

confidence: 82%

Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs

et al. 2020

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“…Urine output was significantly higher in the CRI group. Also K + and Na + excretion were significantly increased in both furosemide groups than in placebo dogs (Hori et al 2010). Our results could be comparable to those of the Hori's study where the hypokalaemia found in both furosemide groups by assumption could be explained by significantly increased kaliuresis.…”

Section: Day 1 Daysupporting

confidence: 87%

“…Studies in veterinary medicine are scarce and most of them performed under experimental conditions on healthy animals. The first reference of such comparison was achieved by Hori in 2009 in healthy anaesthetized dogs, which were aleatory divided into placebo and CRI groups (Hori et al 2010). Furosemide was infused at 0.5 mg/kg/h for 8 h in the CRI group or was injected at 0 and 4 h (2 mg/kg) in the bolus group.…”

Section: Day 1 Daymentioning

confidence: 99%

“…Nowadays, it is widely recognized that the Greyhound breed has unique biological and physiological features differing from those of other breeds of dogs (Vilar et al 2008). In addition, healthy dogs very probably did not have chronic activation of the renin-angiotensin-aldosterone system as is in cardiac patients, thus excreting more water, Na + and retaining K + (Hori et al 2010). Finally, in normal horses, it was demonstrated that CRI furosemide at a dose of 0.12 mg/k/h preceded by a loading dose of 0.12 mg/kg i.v.…”

Section: Day 1 Daymentioning

confidence: 99%

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Comparison of continuous versus intermittent furosemide administration in dogs with acute heart failure

2016

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Pulmonary oedema is a life-threatening condition which should be treated promptly in the emergency room with oxygen, cage rest, and diuretic therapy. Traditionally, bolus administration of furosemide is the treatment of choice. However, there is emerging information that continuous rate infusion might be more effective than bolus injections in relieving clinical signs and producing a lower rate of complications such as azotaemia, dehydration, and electrolyte imbalances. We tested the effect of furosemide both in bolus (4-6 mg/kg intravenously) and continuous rate infusion (1 mg/kg/h) in 30 dogs that had been presented with fulminant pulmonary oedema during 2 days of hospitalization. No differences in the selected biochemical indicators between the groups were found. There were significant differences in blood urea nitrogen in the bolus injection group and creatinine and phosphorus in the continuous rate infusion group between days 1 and 2. The results of this study showed no differences in the approach of furosemide administration in the management of pulmonary oedema. Both methods may cause renal and electrolyte complications, however, further studies with a larger number of patients are recommended. Diuretics, canine, continuous rate infusion, pulmonary oedema

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“…Both PRA and PAC were measured using a radioimmunoassay kit (SRL renin kit; FUJIREBIO Inc, Tokyo, Japan and Spac‐S aldosterone; FUJIREBIO Inc) in accordance with the manufacturer's instructions . All samples were analyzed in duplicate by personnel blinded to dog identity, and the mean values of the data obtained were used for analyses.…”

Section: Methodsmentioning

confidence: 99%

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals

Sakamoto

Sakai

Sato

et al. 2019

Veterinary Internal Medicne

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Background: The renin-angiotensin-aldosterone system (RAAS) is activated in humans with portal hypertension (PH) associated with liver disease. However, involvement of RAAS in dogs with intrahepatic PH is not clear.Objective: To measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in dogs with PH (chronic hepatitis [CH] and primary hypoplasia of the portal vein [PHPV]), dogs with extrahepatic congenital portosystemic shunt (EH-CPSS), and healthy dogs and to determine whether the RAAS is activated in dogs with PH.Animals: Twenty-seven dogs with acquired portosystemic collaterals (APSCs; 15 dogs with CH, 12 dogs with PHPV), 9 dogs with EH-CPSS, and 10 healthy dogs.Methods: Retrospective study. Plasma renin activity and PAC were measured by radioimmunoassay.Results: Plasma renin activity was significantly higher in the CH group (median, 4.4 ng/mL/h) than in the EH-CPSS (median, 1.0 ng/mL/h; P < .01) and the healthy (median, 1.1 ng/mL/h; P < .01) groups. No significant differences were found between the PHPV group (median, 2.2 ng/mL/h) and other groups. Plasma aldosterone concentration was significantly higher in the CH (median, 111.0 pg/mL) and PHPV (median, 89.5 pg/mL) groups than in the EH-CPSS (median, 1.0 pg/mL; P < .001, P < .01, respectively) and healthy (median, 14.5 pg/mL; P < .001, P < .05, respectively) groups.Conclusions and Clinical Importance: Activation of the RAAS contributes to the pathophysiology of intrahepatic PH in dogs, suggesting that spironolactone may not only be effective for the treatment of ascites but also for the suppression of intrahepatic PH. K E Y W O R D S canine, chronic hepatitis, portal hypertension, primary hypoplasia of the portal vein, reninangiotensin-aldosterone system

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Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

Cited by 14 publications

References 33 publications

Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs

Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs

Comparison of continuous versus intermittent furosemide administration in dogs with acute heart failure

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals

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