Mefruside

Abstract: . The effect of mefruside on plasma and muscle electrolytes has been studied in 10 normal subjects and in 8 patients with essential hypertension. The normal subjects, 5 men and 5 women, were given 75 mg (to men) or 50 mg (to women) mefruside daily for one week. The hypertensive patients, who were on normal diet, were treated with 25 mg mefruside daily over a period of 5 months. No extra potassium was supplied. Muscle tissue was obtained by needle biopsy from the m. quadriceps femoris before and after the period of mefruside administration. Tissue samples were analysed for water, sodium, potassium, magnesium, chloride and (in the series of normal subjects) total phosphorus. In the normal subjects a slight hypochloremic, hypokalemic alkalosis was recorded in the plasma; in muscle tissue the total water content decreased, as did the potassium content and the K/P ratio, the decreases averaging 3–4% of the normal mean value. The blood pressure was not changed. Long-term treatment with mefruside in patients with hypertension resulted in a significant blood pressure reduction. Plasma potassium decreased by 0.7 mEq/l; the muscle potassium content was, however, unchanged and the intracellular potassium concentration (calculation based on the chloride method) was significantly increased. The total water content and the intracellular water content (calculation based on the chloride method) was significantly reduced. There was a correlation between the decrease in total water and the change in extracellular water, sodium and chloride content. We conclude that short-term treatment in normal subjects with a high daily dose of mefruside during one week causes a slight depletion of intracellular (muscle) potassium, whereas long-term treatment with a lower dose in hypertensive patients depletes the extracellular fluid potassium without significantly affecting the intracellular content. The reduction in total water and extra- and intracellular water recorded in the hypertensive patients may have a casual relation to the antihypertensive effect.

Abstract: A simple and adequate HPLC method was developed for screening of human urine for the following 17 diuretic drugs: acetazolamide, bendrofluazide, bumetanide, canrenoic acid, chlorothiazide, chlorthalidone, clopamide, epitizide, etacrynic acid, furosemide, hydrochlorothiazide, indapamide, mefruside, piretanide, spironolactone, torasemide, and triamterene. The assay involves extraction from two 2 mL urine samples with ethyl acetate at pH = 5, washing with a phosphate buffer at pH = 6 and analysis by HPLC using a reversed phase C18 column and ultraviolet detection with a diode array detector for all drugs (except triamterene) using two eluents consisting of water, triethylamine, phosphoric acid and acetonitrile at different ratios and different pH values. Triamterene is determined by direct injection of diluted urine onto the column and is measured by fluorescence detection. The recoveries of the diuretic drugs were determined at two different concentrations and ranged from 43–110% (median: 87%) which is sufficient to detect abuse of these drugs. The repeatability of the assay ranged from 1–12% (median: 5.5%).

Abstract: . Systemic BP reduction, calf blood flow and vascular resistance in the calf were determined in forty-two previously untreated patients with mild to moderate essential hypertension (WHO I-WHO II) before and after 6 weeks, 6 months and 18 months of BP-lowering treatment with mefruside (25 mg daily) or atenolol (100–400 mg daily). Blood flow was determined with venous occlusion plethysmography using a mercury-in-rubber strain gauge technique in the supine patient. Auscultatory BP was measured on the right arm simultaneously with the flow determinations and resistance was calculated from the flow and pressure. BP was reduced significantly and to the same extent by the two drugs. In the atenolol group a rise in resting resistance and a corresponding fall in resting blood flow was seen initially. These changes were entirely normalized during continued treatment for 18 months. In the mefruside group no significant haemodynamic changes during treatment were observed at rest apart from the BP fall. None of the drugs reduced resistance at “maximal” vasodilatation, indicating that no regress of the hypertensive structural changes of the calf blood vessels had taken place.

Abstract: The long-term efficacy of nitrendipine and acebutolol was assessed during a 40-week double-blind randomized trial in 60 hypertensive blacks. Nitrendipine (mean dose 32 mg/day) and acebutolol (414 mg/day) were administered in monotherapy in increasing dosage and mefruside was added in patients not controlled by monotherapy. The recumbent and standing blood pressures were reduced (P < 0.01 or less) during monotherapy with nitrendipine and acebutolol, but the magnitude of blood pressure reduction was greater (P < 0.05 or less) during nitrendipine dosing. Pulse rate decreased (P < 0.01) during acebutolol whereas nitrendipine induced a nonsignificant increase. Both treatments induced no changes in serum electrolytes, creatinine, urea, uric acid, lipids, plasma renin activity, and plasma and urinary aldosterone. The overall incidence of side effects was similar with both treatments but four patients discontinued nitrendipine because of headache. The addition of mefruside to nitrendipine or acebutolol produced a further fall of blood pressure in patients not controlled with monotherapy. Monotherapy with nitrendipine or acebutolol offers an effective, safe first-line antihypertensive treatment in blacks entered in this study; with the described dosages and therapeutic schedule, nitrendipine was somewhat more effective than acebutolol. Clinical Pharmacology and Therapeutics (1987) 41, 45–54; doi:10.1038/clpt.1987.7