A010: Kaliuretic potency of thirty-one oral formulations of diuretics: Report on a study series in progress

114A ASH XV ABSTRACTS mg did not modify MM, but they raised MN between 64 and 88%. Roughly, MM paralleled MN after loop and thiazidetype diuretics. MUZ 20 mg and TOR 2.5 mg, both of which are loop diuretics and are provenly effective once-daily antihypertensive monopharmacotherapies, did not raise MM and were the only formulations tested that qualified as very-low-dose formulations, since they did not increase MN. Key Words: Diuretics; magnesium; natriuresis; sodium A009 LACK OF EFFECT OF CICLETANINE ON URIC ACID A.J. Reyes*, W.P. Leary*, and K. van der Byl (deceased). Institute of Cardiovascular Theory, Montevideo, Uruguay, and University College, Cork, Ireland Cicletanine (Ct) is a furopyridine derivative. It is an effective antihypertensive and a distal tubular diuretic. Treatment with Ct has been found not to raise serum uric acid in hypertensive patients. The present study was carried out to evaluate the effects of Ct on the renal handling of UA. Fourteen healthy males, aged 18 –26, in a metabolic unit received placebo (Pl) and Ct 50, 100, and 150 mg once daily, at 8.00 a.m., during four adequately separated single-treatment periods of 7 days each. The design was individually randomized, crossover and double-blind. On days 1 and 7 of each treatment, urine passed 0 –1.5, 1.5–3, 3– 6, 6 –9, 9 –12 and 12–24 h after dosing was collected, and blood was drawn just before and 1.5, 6 and 24 h after dosing. The renal instantaneous fractional excretion (IFE) of UA was evaluated by the standard method. On PI days 1 and 7, 24-h urinary sodium outputs were (mean ⫾ SEM) 156 ⫾ 11 and 177 ⫾ 14 mmol; after Ct 50, 100, and 150 mg, mean values changed by ⫹26% (p ⬍ 0.05 vs. Pl), ⫹38% (p ⬍ 0.001) and ⫹49% (p ⬍ 0.001) on day 1, and by ⫹13%, ⫹12% and ⫹13% on day 7 (p ⬎ 0.05 for each of these three changes). The 24-h urinary output of UA after Pl was 4.2 ⫾ 0.4 and 4.8 ⫾ 0.3 mmol on days 1 and 7, and mean values changed by ⫺11%, ⫹10% and ⫹5% after Ct 50, 100 and 150 mg on day 1 and by ⫺6%, ⫺17% and ⫺9% on day 7 (p ⬎ 0.05 for each of these six changes). Serum UA at 0, 1.5, 6 and 24 h after dosing with Pl was 0.32 ⫾ 0.01, 0.32 ⫾ 0.02, 0.32 ⫾ 0.02 and 0.31 ⫾ 0.02 mmol/L on day 1, and 0.34 ⫾ 0.02, 0.34 ⫾ 0.02, 0.33 ⫾ 0.02 and 0.32 ⫾ 0.02 on day 7. On days 1 and 7 of Ct treatments, serum UA ranged between 0.30 ⫾ 0.02 and 0.35 ⫾ 0.02 mmol/L. None of the Ct mean values of serum UA differed significantly from its Pl mean. At 1.5, 6 and 24 h after dosing with Pl on day 1, the IFE of UA was 10.5 ⫾ 1.4, 8.5 ⫾ 1.1 and 7.8 ⫾ 0.9%; on day 7, it was 8.3 ⫾ 0.6, 7.4 ⫾ 0.5 and 7.9 ⫾ 1.2%. On days 1 and 7 of Ct treatments, the IFE of UA ranged between 6.2 ⫾ 1.0 and 11.7 ⫾ 2.0%. No Ct mean value of the IFE of UA differed significantly from its Pl mean. Ct did not affect the renal handling nor the serum concentration of UA. All common diuretics tested as in this study lowered the fractional excretion of UA and increased uricaemia, even at very low doses. The lack of action of Ct on UA indicates that this chemically distinct antihypertensive and natriuretic is pharmacologically unique. Key Words: Cicletanine; diuretics; natriuresis; UA AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2 A010 KALIURETIC POTENCY OF THIRTY-ONE ORAL FORMULATIONS OF DIURETICS: REPORT ON A STUDY SERIES IN PROGRESS A.J. Reyes* and W.P. Leary*. Institute of Cardiovascular Theory, Montevideo, Uruguay, and University College, Cork, Ireland The changes in mean 24-h kaliuresis (MK) and natriuresis (MN) ensuing single dosing with thirty-one oral formulations of diuretics have thus far been evaluated in nineteen studies, sixteen of which were randomized, crossover, double-blind, and placebo controlled (pre-treatment MK and MN served as control variables in the three open trials). In each study, 7–19 healthy adults staying in a metabolic unit received one (open studies) or more treatments (on conveniently separated single-treatment days). The study series (n ⫽ 223 volunteers) control MK was 49.0 mmol; control MN was 159 mmol. Results refer to changes with respect to control MK and MN in each study. Thiazide-type diuretics: cicletanine 50, 100 and 150 mg did not modify MK (p ⬎ 0.05), but they raised (p ⬍ 0.05) MN by 26, 38 and 49%; clopamide 5 mg, clorexolone 10 mg, chlorthalidone 100 mg, hydrochlorothiazide (HCTZ) 25 mg (which was tested in three studies), HCTZ 50 mg (which was tested in two studies), tizolemide 100 mg, and xipamide 5, 10, 20 and 40 mg increased MK between 18 and 90%, and they elevated MN between 47 and 165%. Loop diuretics: muzolimine (MUZ; this substance is no longer available) 20 and 30 mg, and torasemide (TOR) 2.5 and 5 mg did not change MK; MUZ 20 mg and TOR 2.5 mg did not modify MN either, whereas MUZ 30 mg and TOR 5 mg raised MN by 33 and 22%; furosemide (FUR) 80 mg, MUZ 40 mg, piretanide 12 mg, TOR 10 mg, and TOR 20 mg raised MK by 38, 50, 35, 15, and 29%, and they raised MN between 17 and 86%. Potassiumretaining diuretics: amiloride (AMI) 5 and 10 mg reduced MK by 28 and 32%, and they increased MN by 38 and 66%; spironolactone (SPIR) 100 mg did not change MK nor MN. Combinations: FUR 40 mg & AMI 5 mg, FUR 80 mg & AMI 10 mg, HCTZ 50 mg & AMI 5 mg, HCTZ 100 mg & AMI 10 mg, HCTZ 50 mg & triamterene 100 mg, and HCTZ 25 mg & SPIR 100 mg did not modify MK, but they raised MN by 75, 64, 70, 138, 95 and 88%. MUZ 20 mg and TOR 2.5 mg, which are provenly effective once-daily antihypertensives, were the only formulations tested did not raise MK and that also qualified as very-low-dose formulations of diuretics since they did not raise MN. Key Words: Diuretics; kaliuresis; natriuresis; potassium A011 THE RESEARCH OF VENTRICULAR REMODELING BY SCUTELLAREIN TREATMENT IN SPONTANEOUS HYPERTENSIVE RATS J.Z. Zhou, H. Lei*, Y.Z. Chen, and F.q. Li. Department of Internal Medicine, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, P.R. China Protein Kinase C (PKC) is an important link factor in passing messages of cell and Scutellarein has been proved to be a kind of PKC inhabitors. It decreases blood pressure (BP) in large doses. Therefore we assume that Scutellarein would  (...truncated)