Pharmacokinetic and Pharmacodynamic Interactions between Furosemide and Hydrochlorothiazide in Nephrotic Patients

Abstract

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.

The influence of gastrointestinal transit on drug absorption in healthy volunteers.

“…The absorption of atenolol, hydrochlorothiazide and frusemide is relatively slow and incomplete whereas the absorption of salicylic acid is rapid and complete (Beerman & Groschinsky-Grind, 1977;Mason et al, 1979;Needs & Brooks, 1985;Waller et al, 1985). There is no evidence of drug interactions within the group (Miners, 1989;Nakahama et al, 1988;Sabanathan et al, 1987) and all, with the exception of salicylic acid, are excreted largely unchanged in the urine so that cumulative urinary excretion may be used as an index of the extent of absorption. Although salicylic acid is extensively metabolised, total urinary salicylate is a quantitative measure of the amount of salicylic acid absorbed.…”

The Na+-excreting efficacy of indapamide in combination with furosemide in massive edema

“…2 Furosemide blocks the Na + -K + -2Cl -symporter in the thick ascending limb of the loop of Henle, and the use of a combination of a loop diuretic and a thiazide is recommended in such furosemide-resistant edema, because thiazides suppress Na + reabsorption in the distal convoluted tubules. 3 However, thiazides are known to occasionally induce metabolic abnormalities, such as hyperglycemia and hyperlipidemia. Although a combination therapy of furosemide and metolazone is recommended, 4 metolazone is not available in Japan.…”

Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome

“…(27,29,33) Our current knowledgebase of hypothetical mechanisms underlying kidney sodium avidity and resultant DR relies primarily on animal models or human studies performed in euvolemic healthy controls and patients with hypertension or chronic kidney disease. (34)(35)(36)(37)(38)(39)(40) Although chronic kidney disease is a co-morbid condition in up to one-half of patients with HF, diminished GFR and the systemic aberrations appear to have less of a prominent role on natriuresis and diuretic response in CRS. (41) There is a paucity of studies in patients with CRS on contemporary medical therapy, and DR mechanisms appear to differ based on the clinical context and population.…”