Eur J Clin Pharmacol (1987) 33:515-517 European Journal of Clinical Pharmacology © Springer-Verlag 1987 Metabolic Effects of Long-Term Therapy with Muzolimine and Chlorthalidone in Hypertension F. Galletti 1, R Strazzullo 1, R. Gagliardi 2, M. Cirillo I, A. SianP, R. Iacone ~, M. Mancini ~ 1 Institute of Internal Medicine and Metabolic Diseases, 2nd Medical School, University of Naples, and z Medical Department, Bayer, Italy Summary. Previous short-term studies of muzoli- mine (a diuretic with frusemide-like activity) had shown that it did not induce a significant change in the serum potassium concentration. In the present study sodium and potassium handling and other metabolic variables have been compared during 16 weeks of therapy with muzolimine and chlorthal- idone, a thiazide-like diuretic. During muzolimine treatment, plasma and red cell potassium concentra- tions remained unchanged, while a significant fall in potassium occured with chlorthalidone. Neither drug affected the activity of sodium-potassium co- transport or sodium-lithium countertransport in red cells in vitro. Muzolimine and chlorthalidone had similar effects on arterial pressure and on the other metabolic variables tested. Key words: muzolimine, chlorthalidone; hyperten- sion, serum electrolytes, potassium, ion transport Muzolimine is a long-acting diuretic with fruse- mide-like activity [1-3], which can reduce the blood pressure [4, 5]. In previous short-term trials, muzoli- mine did not induce a significant decrease in the se- rum potassium concentration [6-8]. The present study was undertaken to evaluate the long-term ef- fects of muzolimine on blood pressure and several metabolic variables, including serum and red cell potassium concentrations. Muzolimine was com- pared with chlorthalidone, a thiazide-like diuretic widely used in the treatment of arterial hypertension [91. Materials and Methods Twenty untreated hypertensive patients referred to the Hypertension Clinic were studied, after a wash- out period of 2 weeks (ages 25-65 years, WHO Class 1-11). The patients were randomly allocated either to muzolimine 30 mg once a day or chlorthal- idone 25 mg once a day for 16 weeks. The study was of open design, but the investigator who mea- sured the blood pressures was blind to the treat- ments. Supine and standing blood pressure, resting heart rate, and plasma sodium and potassium were determined at the beginning and after 2, 4, 8, 12, and 16 weeks of treatment. Red cell sodium and po- tassium concentrations and in vitro sodium-lithium countertransport and sodium-potassium co-trans- port were measured at baseline and after 8 and 16 weeks of treatment. Plasma renin activity (PRA), glomerular filtra- tion rate estimated by creatinine clearance (GFR), serum uric acid, plasma triglyceride (Tg), and HDL- cholesterol: total cholesterol ratio were determined at baseline and at the end of the study. At the same times an oral glucose tolerance test (OGTI', 75 g glucose as a 33% solution) was performed with the patient on an unrestricted diet with liberal carbohy- drate intake. Systolic and Phase V diastolic pres- sures were measured after a t0-min rest, twice in the supine position and twice after standing for 2 min. Mean arterial pressure (MAP) was calculated as the sum of the diastolic pressure and ½ of the pulse pressure. PRA and plasma insulin concentrations (IRI) were measured by radioimmunoassay. Red celt so-