Effect of tienilic acid and amiloride in healthy volunteers and in hypertensives with normal renal function.

Jb, Myers; Gillies, Alastair J.; Waga, Shinobu; Morgan, T. O.

doi:10.1111/j.1365-2125.1980.tb01770.x

Cited by 4 publications

(2 citation statements)

References 23 publications

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“…A tendency to increased plasma uric acid concentration was observed b y the end of each medication period. This is in accordance with previous short-term studies which have shown that thiazide diuretics increase serum uric acid concentrations already after a few weeks of use (17,18,22). Amiloride alone seems not to influence uric acid values (6, 17, 18) a n d triamterene has equally been claimed not to cause hyperuricaemia (14).…”

Section: Discussionsupporting

confidence: 91%

Effect of Low Dose Diuretics on Plasma and Blood Cell Electrolytes, Plasma Uric Acid and Blood Glucose

Sundberg¹,

Salo²,

Gordin³

et al. 1982

Journal of Internal Medicine

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ABSTRACT. The short‐term effects of three diuretic drug regimens on plasma and blood cell electrolytes, plasma uric acid and blood glucose were studied in 11 subjects (aged 35–62 years) with mild hypertension in a double‐blind cross‐over study. Blood cell electrolytes were determined from hemolysed whole blood. The subjects were given 25 mg of hydrochlorothiazide (H), a combination of 25 mg of H and 2.5 mg of amiloride (HA) or a combination of 25 mg of H and 37.5 mg of triamterene (HT) once daily for 4 weeks in a randomized order. Plasma potassium fell slightly from 4.2–4.1 to 4.0–3.9 on each drug (significantly on H and HT, p < 0.05), the drop being most marked after one week. There were no statistically significant differences between the drug regimens. No changes were observed in plasma magnesium, calcium or sodium concentrations during the treatment periods. No statistically significant changes occurred in blood cell potassium or magnesium during any of the diuretic regimens. The increases in blood glucose during the treatment periods were minor, but this was statistically significant (p < 0.05) on HT. Plasma uric acid increased slightly but statistically significantly on each drug regimen (p < 0.05 on H and HA, p < 0.01 on HT). Three subjects who originally had normal or borderline uric acid values became clearly hyperuricaemic on each drug. All drug regimens decreased the systolic and diastolic blood pressure almost equally effectively. It is concluded that the 3 diuretic drug regimens had no clinically significant short‐term effects on plasma electrolytes. However, it is probable that hyperuricaemia cannot be avoided in predisposed subjects even when diuretics are used in low doses.

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Section: Discussionsupporting

confidence: 91%

Effect of Low Dose Diuretics on Plasma and Blood Cell Electrolytes, Plasma Uric Acid and Blood Glucose

Sundberg¹,

Salo²,

Gordin³

et al. 1982

Journal of Internal Medicine

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“…A significant fall in standing systolic blood pressure occurred within 24 h after IND and within 48 h after HCTZ (Figure 3). Previous metabolic studies with IND (Irvin et al, 1978) tienilic acid and HCTZ (Sullivan et al, 1978;Myers et al, 1980) were unable to demonstrate blood pressure changes in volunteers. Our positive findings may reflect the longer (6 days) period of dietary equilibration and hospitalization of subjects, which provided more stable 'base-line' parameters.…”

Section: Metabolic Studymentioning

confidence: 92%

Untitled

1984

Brit J Clinical Pharma

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The effects of indacrinone (IND) have been investigated in a two part study. First, a total of 36 clearance studies have been performed in 14 healthy volunteers, under conditions of either maximal hydration or hydropenia, to compare the renal sites of action of single oral doses of IND, 20 mg, ethacrynic acid (EA), 100 mg, and hydrochorothiazide (HCTZ), 100 mg. 2 Under conditions of maximal water hydration, IND increased fractional Na+ excretion from a mean of 1.19 + 0.05 to 4.93 + 0.67% of GFR. This was similar to the response seen with HCTZ, which increased fractional Na+ clearance up to 3.16 + 0.17% of GFR; EA increased fractional Na+ excretion up to 14.5 + 2.5% of GFR. The mean reduction in fractional free-water clearance (CH2O/ GFR x 100%) invoked by IND, (A =-34.8% of control) was similar to that produced by EA, (A =-27.2% of control), and by HCTZ, (A =-26.6% of control). 3 During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TCH2O/GFR x 100%), AIND =-20.3% of control, AEA =-70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, AHCTZ =-20.7% of control. 4 In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 + 0.1 to 15.2 + 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 + 0.03 to 0.34 + 0.03 mM (P < 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. 5 In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. 6 Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and P04 3excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. 7 Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days. HCTZ caused small reductions in fractional urate excretion during the first 4 h after each daily administration: however, plasma urate concentrations remained significantly elevated throughout the study, rising from a mean pre-drug value of 0.35 + 0.01 to 0.44 + 0.01 mM (P < 0.05) after 8 days of therapy.

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Renal actions of a uricosuric diuretic, racemic indacrinone, in man: comparison with ethacrynic acid and hydrochlorothiazide.

Brooks¹,

Lant²,

McNabb³

et al. 1984

Brit J Clinical Pharma

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3 During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TCH2O/GFR x 100%), AIND = -20.3% of control, AEA = -70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, AHCTZ = -20.7% of control. 4 In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 + 0.1 to 15.2 + 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 + 0.03 to 0.34 + 0.03 mM (P < 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. 5 In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. 6 Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and P04 3-excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. 7 Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days. HCTZ caused small reductions in fractional urate excretion during the first 4 h after each daily administration: however, plasma urate concentrations remained significantly elevated throughout the study, rising from a mean pre-drug value of 0.35 + 0.01 to 0.44 + 0.01 mM (P < 0.05) after 8 days of therapy.Keywords indacrinone ethacrynic acid hydrochorothiazide diuretics 497

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Effect of tienilic acid and amiloride in healthy volunteers and in hypertensives with normal renal function.

Cited by 4 publications

References 23 publications

Effect of Low Dose Diuretics on Plasma and Blood Cell Electrolytes, Plasma Uric Acid and Blood Glucose

Effect of Low Dose Diuretics on Plasma and Blood Cell Electrolytes, Plasma Uric Acid and Blood Glucose

Untitled

Renal actions of a uricosuric diuretic, racemic indacrinone, in man: comparison with ethacrynic acid and hydrochlorothiazide.

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