The Effect of Intravenous Infusion Time on the Pharmacokinetics and Pharmacodynamics of the Same Total Dose of Azosemide in Rabbits

Park, Kwang J.; Yoon, Woo H.; Shin, Wonjae; Lee, Myung G.

doi:10.1002/(sici)1099-081x(199701)18:1<41::aid-bdd1>3.0.co;2-m

Cited by 9 publications

(10 citation statements)

References 16 publications

(22 reference statements)

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“…This clearly illustrates the importance of the composition of the fluid used for replacement. Similar results have been reported with furosemide , bumetanide (Yoon et al 1995) and azosemide (Park et al 1997b). Second, both treatments 1 and 4 received no sodium replacement and there was no significant difference in the A e 0±8 h of torasemide (Table 1).…”

Section: Discussionsupporting

confidence: 82%

“…This indicates that water replacement (the rate of fluid replacement from zero to 100%) per se may have significant effects on diuresis, natriuresis and chloruresis, even though sodium intake is zero or perhaps minimal. Different results have been reported with furosemide , bumetanide (Yoon et al 1995) and azosemide (Park et al 1997b). If the present study in rabbits can be directly extrapolated to patients receiving zero-order input of torasemide, then more negative sodium and chloride balance can both be achieved as long as the patients receive the same amount of water that is lost from the body.…”

Section: Discussionmentioning

confidence: 49%

“…The significantly larger urine output in treatment 3 could be owing to significantly greater A e 0±8 h and the significantly higher diuretic efficiency in treatment 3 (Table 1). The acute time-dependent tolerance of furosemide , bumetanide (Yoon et al 1995) and azosemide (Park et al 1997b) was owing to incomplete replacement of fluid. This was also shown with torasemide.…”

Section: Discussionmentioning

confidence: 99%

“…Since the importance of fluid or electrolyte replacement for urine loss in the evaluation of diuretics was recognized (Earley & Martino 1970;Branch et al 1977;Homeida et al 1979;Kahn et al 1983;Wilcox et al 1983;Hammarlund et al 1985), quantitative aspects of the effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of furosemide , bumetanide (Yoon et al 1995) and azosemide (Park et al 1997b) loop diuretics have been reported. The pharmacodynamics (urine output and urinary excretion of sodium) of furosemide , bumetanide (Yoon et al 1985) and azosemide (Park et al 1997b) were significantly different with different rates and compositions of fluid replacement in dogs and rabbits (Yoon et al 1995;Park et al 1997b). A review of the literature on torasemide indicated considerable inconsistencies among various studies.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, lactated Ringer's solution was continuously infused at a rate of 10 mL kg ¡1 h ¡1 (Dubourg et al 2000). It might be anticipated from studies of furosemide , bumetanide (Yoon et al 1995) and azosemide (Park et al 1997b) that if the rate and/or the composition of fluid replacement are critical, the inconsistencies mentioned above might have led to different interpretations or conclusions in the evaluation of the pharmacokinetics and/or pharmacodynamics of torasemide.…”

Section: Introductionmentioning

confidence: 99%

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Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous torasemide

Kim

Lee

et al. 2003

Journal of Pharmacy and Pharmacology

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The effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of torasemide were evaluated in rabbits. Each rabbit received 2-h constant intravenous infusion of 1 mg kg(-1) torasemide with 0% replacement (treatment 1, n=6), 50% replacement (treatment 2, n=9), 100% replacement with lactated Ringer's solution (treatment 3, n=8), and 100% replacement with 5% dextrose in water (treatment 4, n=6). Total body (4.53, 5.72, 10.0 and 4.45 mL min(-1) kg(-1) for treatments 1-4, respectively) and renal clearance (1.44, 1.87, 6.78 and 1.72 mL min(-1) kg(-1)) of torasemide, and total amount of unchanged torasemide excreted in 8-h urine (A(e 0-8 h): 694, 780, 1310 and 1040 microg) in treatment 3 were considerably faster and greater compared with treatments 1, 2 and 4. Although the difference in A(e 0-8 h) between treatments 1 and 3 was only 88.8%, the diuretic and/or natriuretic effects of torasemide were markedly different among the four treatments. For example, the mean 8-h urine output was 101, 185, 808 and 589 mL for treatments 1-4, respectively, and the corresponding values for sodium excretion were 10.1, 20.6, 89.2 and 29.9 mmol, and for chloride excretion were 14.5, 27.9, 94.0 and 37.2 mmol. Although full fluid replacement was used in both treatments 3 and 4, the 8-h diuretic, natriuretic and chloruretic effects in treatment 3 were significantly greater compared with treatment 4, indicating the importance of the composition of fluid replacement. Both treatments 1 and 4 received no sodium replacement, however, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 4 compared with treatment 1, indicating the importance of rate of fluid replacement for the diuretic effects. Therefore, the 8-h diuretic, natriuretic and chloruretic effects were significantly greater in treatment 3 compared with treatments 1, 2 and 4, indicating the importance of full fluid and electrolyte replacement. Some implications for the bioequivalence evaluation of dosage forms of torasemide are discussed.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous torasemide

Kim

Lee

et al. 2003

Journal of Pharmacy and Pharmacology

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Pharmacokinetics and pharmacodynamics of azosemide

Suh¹,

Kim²,

Lee³

2003

Biopharm & Drug Disp

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Azosemide is used in the treatment of oedematous states and hypertension. The exact mechanism of action is not fully understood, but it mainly acts on both the medullary and cortical segments of the thick ascending limb of the loop of Henle. Delayed tolerance was demonstrated in humans by homeostatic mechanisms (principally an increase in aldosterone secretion and perhaps also an increase in the reabsorption of solute in the proximal tubule). After oral administration to healthy humans in the fasting state, the plasma concentration of azosemide reached its peak at 3-4 h with an absorption lag time of approximately 1 h and a terminal half-life of 2-3 h. The estimated extent of absolute oral bioavailability in humans was approximately 20.4%. After oral administration of the same dose of azosemide and furosemide, the diuretic effect was similar between the two drugs, but after intravenous administration, the effect of azosemide was 5.5-8 times greater than that in furosemide. This could be due to the considerable first-pass effect of azosemide. The protein binding to 4% human serum albumin was greater than 95% at azosemide concentrations ranging from 10 to 100 microg/ml using an equilibrium dialysis technique. The poor affinity of human tissues to azosemide was supported by the relatively small value of the apparent post-pseudodistribution volume of distribution (Vdbeta), 0.262 l/kg. Eleven metabolites (including degraded products) of azosemide including M1, glucuronide conjugates of both M1 and azosemide, thiophenemethanol, thiophencarboxylic acid and its glycine conjugate were obtained in rats. Only azosemide and its glucuronide were detected in humans. In humans, total body clearance, renal clearance and terminal half-life of azosemide were 112 ml/min, 41.6 ml/min and 2.03 h, respectively. Azosemide is actively secreted in the renal proximal tubule possibly via nonspecific organic acid secretory pathway in humans. Thus, the amount of azosemide that reaches its site of action could be significantly modified by changes in the capacity of this transport system. This capacity, in turn, could be predictably changed in disease states, resulting in decreased delivery of the diuretic to the transport site, as well as in the presence of other organic acids such as nonsteroidal anti-inflammatory drugs which could compete for active transport of azosemide. The urinary excretion rate of azosemide could be correlated well to its diuretic effects since the receptors are located in the loop of Henle. The diuretic effects of azosemide were dependent on the rate and composition of fluid replacement in rabbits; therefore, this factor should be considered in the evaluation of bioequivalence assessment.

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Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

Kim

Lee

et al. 2004

Biopharm & Drug Disp

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The pharmacokinetics and pharmacodynamics of torasemide were evaluated after intravenous administration of the same total dose of torasemide at a dose of 1mg/kg to rabbits with different infusion times, 1 min (treatment I), 30 min (treatment II) and 2 h (treatment III). The loss of water and electrolytes in urine induced by torasemide was immediately replaced with infusion of an equal volume of lactated Ringer's solution. All the pharmacokinetic parameters of torasemide, such as total area under the plasma concentration-time curve from time zero to time infinity (AUC), total body clearance (CL), apparent volume of distribution at steady state (Vss), terminal half-life and mean residence time (MRT), were independent of infusion times. However, the 8 h urine output (235, 534 and 808 ml) and 8 h urinary excretion of sodium (24.2, 80.1 and 89.2 mmol) and chloride (27.1, 89.2 and 94.0 mmol) were significantly greater in treatments II and III than those in treatment I, although the total 8 h urinary excretion of unchanged torasemide (1210, 1210 and 1310 microg) were not significantly different among the three treatments. This could be due to the higher diuretic efficiencies in treatments II and III.

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The Effect of Intravenous Infusion Time on the Pharmacokinetics and Pharmacodynamics of the Same Total Dose of Azosemide in Rabbits

Cited by 9 publications

References 16 publications

Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous torasemide

Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous torasemide

Pharmacokinetics and pharmacodynamics of azosemide

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of torasemide in rabbits

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