Pharmacodynamics and pharmacokinetics of furosemide combinations with potassium-retaining and thiazide-like diuretics: Clearance and micropuncture studies

Hropot, M.; Sörgel, Fritz; Mutschler, E.

doi:10.1007/bf00500025

Cited by 8 publications

(8 citation statements)

References 11 publications

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“…Therefore, there is a possibility that hydroch lorothiazide could competitively inhibit transport of such weak acids as furosemide. This hypothesis was supported by Hropot et al [7], They proposed that, using free-flow micropuncture studies in rats, hydrochlorothi azide significantly decreased the urinary furosemide se cretion and increased the plasma furosemide concentra tion, thus prolonging the salidiuretic effect.…”

Section: Discussionsupporting

confidence: 69%

“…Isolated clinical reports are frequent, but only a few well-monitored studies are available [5][6][7].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, those studies have been performed only in animals or in normal volunteers [5][6][7]. Therefore, the purpose o f the present investigation was to establish whether hydroch lorothiazide, one o f the most commonly used thiazidetype diuretics, changes the pharmacokinetics o f furose mide and by this mechanism enhances the diuretic effect in nephrotic patients.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic and Pharmacodynamic Interactions between Furosemide and Hydrochlorothiazide in Nephrotic Patients

Nakahama

Orita

Yamazaki

et al. 1988

Nephron

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We examined the response of 8 patients with nephrotic syndrome (creatinine clearance 70.4 ± 16.0 ml/ min) to oral furosemide (F; 40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT; 100 mg). In the 24-hour period after oral F, HCT was shown to increase urine volume and urinary sodium and chloride excretion. Increment was most significant during the 12- to 24- hour period. Enhancement of the diuresis with HCT was associated neither with a significant increase in the area under the curve of plasma F concentration nor an increase in urinary F excretion. Urinary excretion of glucuronidated F, one of the main metabolites of F, however, was decreased with HCT. In summary, HCT significantly enhanced the response to F in nephrotic patients.

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Section: Discussionsupporting

confidence: 69%

“…Isolated clinical reports are frequent, but only a few well-monitored studies are available [5][6][7].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic and Pharmacodynamic Interactions between Furosemide and Hydrochlorothiazide in Nephrotic Patients

Nakahama

Orita

Yamazaki

et al. 1988

Nephron

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“…Three patients were, for short periods, prescribed bumetanide alone (results not included in analysis) and seven patients received amiloride in addition to furosemide at some point, in the form of combination treatment (co‐amilofruse = furosemide 40 mg + amiloride 5 mg). This combination does not affect total natriuresis during chronic dosing and therefore does not affect the interpretation of furosemide responsiveness [18]. Three patients received additional spironolactone and one had short‐term bendrofluazide in addition to loop diuretic (these results are not included in analysis).…”

Section: Resultsmentioning

confidence: 99%

Furosemide responsiveness, non‐adherence and resistance during the chronic treatment of heart failure: a longitudinal study

MacFadyen¹,

Gorski²,

Brater³

et al. 2004

Brit J Clinical Pharma

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Background and methodsLoop diuretic therapy is an essential part of chronic systolic heart failure (CH)F management, yet response to treatment can be variable. We analysed diuretic responsiveness in 39 stable patients with CHF in the community over 2 years. We measured serum ACE as a marker of adherence to ACE inhibitor therapy and urinary furosemide as a marker of diuretic adherence and action. Patients' clinical outcome was stable and not hospitalized (Group 0); alive but hospitalized (Group 1); or dead during follow up (Group 2). ResultsPrescribed furosemide dose was variable (range 20-370 mg generally once daily) and progressive dose increments were common. Failed furosemide adherence (defined as < 10% of a dose excreted in 24 h urine where normal average excretion = 50% of an oral dose) during static prescribed dosing was infrequent relative to all days of therapy; yet was equally common across all outcome g roups. Furosemide non-adherence appeared to be independent of non-adherence with ACE inhibitor (as marked by serum ACE activity > 20 U l -1 ) treatment. Furosemide responsiveness (m M of sodium excreted per mg furosemide in urine) showed no relationship to prescribed dose and paradoxically tended to rise in patients with higher basal aldosterone concentrations. Furosemide responsiveness fell by outcome class despite increased dose. Within-patient responsiveness remained relatively constant although highly variable between individuals. ConclusionsFurosemide responsiveness varied greatly between individuals but was constant within an individual. Non-adherence with furosemide was less common among those who died and appeared to occur at different time points from non-adherence with ACE inhibitor treatment, which was slightly more common in all outcome g roups. Patients who died were prescribed higher furosemide doses and had g reater furosemide excretion yet had similar sodium excretion. The main factor in response to chronic furosemide therapy was intrarenal diuretic resistance. Gross non-adherence was less important.Furosemide in the chronic treatment of heart failure Br J Clin Pharmacol 57 :5 623

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“…The combination of furosemide and a thiazide diuretic (i.e. chlorothiazide or hydrochlorothiazide) has been shown to increase the natriuresis compared with that induced by furosemide alone in animal models 1 . Furthermore, the combination of loop diuretic and a thiazide diuretic has been shown to increase the natriuresis compared with that induced by furosemide alone in addition to increasing the amount of weight loss in adult heart failure and fluid overloaded patients 2-5 .…”

Section: Introductionmentioning

confidence: 99%

Stability of furosemide and chlorothiazide stored in syringes

Cies

Moore

et al. 2015

American Journal of Health-System Pharmacy

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PURPOSE Furosemide is a loop diuretic and chlorothiazide is a thiazide diuretic which are commonly used in pediatric patients for varying reasons. Furosemide and chlorothiazide can be used concomitantly to maximize diuresis. It has been a practice at some institutions to combine furosemide and chlorothiazide in the same syringe even though stability data is currently lacking for this combination. The purpose of this study was to determine whether furosemide and chlorothiazide are stable either alone or when mixed together. METHODS Chlorothiazide and furosemide were diluted in 5% dextrose USP to a final concentration of 10 mg/mL of chlorothiazide and 1 mg/mL of furosemide and combined. Samples of chlorothiazide in dextrose, furosemide in dextrose and dextrose alone were also prepared for control purposes. Compounds were detected using an Agilent 6460 Triple Quad LC/MS/MS equipped with an ESI source. RESULTS Chlorothiazide typically eluted from the chromatogram at 2.6 min and furosemide at 4.8 min. Mixtures and samples were diluted 10,000 fold prior to LC/MS/MS analysis to give 1,000 ng/mL chlorothiazide and 100 ng/mL furosemide so that both would be in the linear range of the assay. Each compound was degraded by exposure to strong UV light in a time-dependent manner. Both chlorothiazide and furosemide retained over 90% of the original concentration when stored separately or together for up to 96 h. CONCLUSIONS Chlorothiazide (10 mg/mL) and furosemide (1 mg/mL) are stable for up to 96 hours at room temperature when protected from light, either alone or together in dextrose 5%.

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Pharmacodynamics and pharmacokinetics of furosemide combinations with potassium-retaining and thiazide-like diuretics: Clearance and micropuncture studies

Cited by 8 publications

References 11 publications

Pharmacokinetic and Pharmacodynamic Interactions between Furosemide and Hydrochlorothiazide in Nephrotic Patients

Pharmacokinetic and Pharmacodynamic Interactions between Furosemide and Hydrochlorothiazide in Nephrotic Patients

Furosemide responsiveness, non‐adherence and resistance during the chronic treatment of heart failure: a longitudinal study

Stability of furosemide and chlorothiazide stored in syringes

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