Lack of pharmacodynamic interactions between acute dose flosequinan and xamoterol

The possible cardiovascular pharmacodynamic interactions at rest and during exercise of combining oral flosequinan (100 mg) with xamoterol (200 mg) was investigated in a four-way randomised double-blind placebo-controlled crossover trial in eight healthy male volunteers.Xamoterol was better tolerated than flosequinan. The most common adverse events were mild to moderate headache and facial flushing. One volunteer developed headache and vomiting following flosequinan treatment and was replaced. Compared to placebo, at supine rest, flosequinan significantly increased heart rate (HR) by 5 beats·min^v1, but had no effect on cardiac output (CO), stroke volume (SV) and mean blood pressure (MBP). Xamoterol significantly increased CO by 1.5 l·min^-1, HR (5 beats·min^-1) and MBP (6 mmHg) but not SV. The combined treatment (flosequinan + xamoterol) significantly increased CO (1.71·min^-1) and HR (10 beats·min^-1), but had no effect on SV and MBP. During exercise, flosequinan had no significant effect on any variable compared to placebo. Both xamoterol and combined treatment reduced the increase in CO (-4.61·min^-1 after xamoterol and -3.41·min^-1 after combined treatment vs. 0.1 l·min^-1 after placebo), but had no effect on other variables.The effect of the combined treatment on each haemodynamic variable were no more than the anticipated additive effects of the two drugs. Thus, no cardiovascular pharmacodynamic interaction was found between flosequinan and xamoterol in healthy volunteers.     

Acute effects of felodipine and nifedipine on hepatic and forearm blood flow in healthy men

Summary The acute effects of oral administration of felodipine 10 mg and nifedipine 10 mg on heart rate, blood pressure, forearm blood flow and hepatic blood flow were studied in nine healthy men.Both drugs caused an increase in heart rate of 16 and 7 beats · min^–1, respectively. Hepatic blood flow was significantly increased by 1.2 and 0.41 · min^–1 after felodipine and nifedipine. There was also a decrease in diastolic blood pressure, 10 and 5 mm Hg, respectively, after felodipine and nifedipine. The forearm blood flow was increased by about 30 ml · 100 ml^–1 · min^–1 after felodipine, but nifedipine had no effect.The haemodynamic effects were most pronounced 50 min after drug administration.     

Acute haemodynamic and neurohumoral effects of intravenous nisoldipine in patients with severe congestive heart failure

Summary Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continous infusion of 0.2 g · kg^–1 · min^–1. Haemodynamic measurements were performed at baseline and after 30 min.The mean arterial pressure fell from 91 to 73 mm Hg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn · s · cm^–5.The cardiac index (2.2 to 2.71 · min^–1 · m^–2, and stroke volume index (25 to 33 ml · m^–2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats · min^–1. Plasma renin activity and norepinephrine concentration did not change significantly.The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology.     

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response

Summary The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51–90 ml · min^–1; II 26–50 ml · min^–1; III 4–25 ml · min^–1.The area under plasma level time curve AUC, the elimination half-life t/12, the maximum plasma concentration C_max, the time to peak concentration t_max were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine A_e and the renal clearance CL_R of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.     

The pharmacokinetics and haemodynamic effects of continuous nicorandil infusion in healthy volunteers

Summary We have studied the pharmacokinetics and haemodynamic effects of nicorandil after a 12-h infusion. Nicorandil is a mixed vasodilator combining the actions of a nitrate and a potassium channel opener.Nicorandil was infused for 12 h in 21 healthy volunteers at rates of 0.05, 0.10, and 0.20 g·kg^–1·min^–1 using a placebo controlled, crossover design. Systemic blood pressure, heart rate, electrocardiographic (ECG) intervals, and cardiac output (impedance cardiography) were measured supine and standing.Dose-related, steady-state plasma nicorandil concentrations occurred within 3 to 4 h. Nicorandil's pharmacokinetics were linear with dose.Four 0.20 g·kg^–1·min^–1 nicorandil infusions were terminated early primarily because of moderate or severe headaches. There were no safety concerns (ECG intervals, laboratory assays).Blood pressure fell versus placebo only in the standing position and heart rate increased slightly (not significant). That is, standing blood pressure in the 6 to 12 h interval fell from baseline 8.0*/6.8, 1.6/5.1, and 9.8*/7.9* mmHg (systolic/diastolic, *=P<0.05 versus placebo) at 0.05, 0.10, and 0.20 g·kg^–1·min^–1 respectively. Cardiac output increased slightly above placebo at lower doses. Haemodynamic changes correlated poorly with plasma nicorandil concentrations. Similar total doses were less well-tolerated when extended over 12 h. We saw no evidence of pharmacodynamic tolerance to nicorandil within 12 h.     

Pharmacokinetics of bendroflumethiazide in hypertensive patients

Summary After four weeks on placebo treatment, 8 hypertensive patients (WHO stage I) were treated for 2 weeks with bendroflumethiazide (bft) 2.5 mg and KCl 1.5 g daily. Subsequently they received bft 5 mg and KCl 1.5 g daily for a further fortnight. At the end of each period of treatment blood pressure was recorded and blood samples and urine were collected for analysis of bft by GLC. Before taking the daily dose of bft, no trace of the drug was found in plasma. Peak levels of bft were seen after 2.3 h and averaged 23 and 50 ng · ml^–1 after 2.5 and 5 mg, respectively. After bft 2.5 mg the plasma level was too low for kinetic analysis. The plasma half-life after 5 mg averaged 4.1 h. The mean apparent volume of distribution was 1.18 l · kg^–1. Non-renal clearance averaged 200 ml · min^–1. The renal clearance of bft was significantly lower (p<0.05) after 5 mg (48 ml · min^–1) than after 2.5 mg bft (93 ml · min^–1), although the creatinine clearance remained unchanged. No correlation was found between the plasma level of bft and its effect on blood pressure.Supported by the Swedish Medical Research Council (Grant No. B77-19X-00227-13) and Ferrosan AB, Malmö, Sweden.     

The acute haemodynamic effects of nicardipine in patients with chronic left ventricular failure

Summary Nicardipine is a new slow channel calcium blocker. It has been shown to be effective in the treatment of hypertension and angina pectoris. Nine patients with mild to moderate left ventricular failure were given intravenous infusions of nicardipine and the haemodynamic effects measured. In patients receiving 20 mg of nicardipine, mean cardiac index rose to a peak 1.8 l·min^–1·m^–2 (64%) above the preinfusion level, stroke volume index rose by 12 ml·m^–2 (35%) and heart rate rose by 16 beats·min^–1 (20%). There was a significant fall in systemic vascular resistance of 50% manifested by a reduction of 22 mm Hg in systolic blood pressure (18%) and 18 mm Hg in diastolic blood pressure (22%). Pulmonary vascular resistance fell by 45%. Mean pulmonary artery pressure and capillary wedge pressure did not change significantly. This study suggests that concomitant mild to moderate left ventricular failure is not a contra-indication to nicardipine therapy in patients with angina.     

Human renovascular effects of dopexamine hydrochloride: A novel agonist of peripheral dopamine and beta2-adreno-receptors

Summary The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity.Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B)=504 ml·min^–1; after treatment (D)=605 ml·min^–1), CO (B=5.9 l·min^–1; D=6.7 l·min^–1), heart rate (B=77 beats/min; D=100 beats/min) and systolic blood pressure (B=143 mmHg; D=166 mmHg) were observed on administration of dopexamine 3 µg·kg^–1·min^–1, with insignificant changes in diastolic blood pressure (B=84.4 mmHg; D=90 mmHg) and total peripheral resistance (B=17.85; D=17.25 Units). There was a slight but significant reduction in renal vascular resistance (B=20.59, D=18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B=8.5%, D=9%), consistent with selective renal vasodilation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA₁-receptor mediated effect.European Exchange Senior House Office supported by EEC fellowship 1985 Ospedale Maggiore, Milano, Italy     

Hemodynamic effects of Ro 23-6152 in patients with essential hypertension

Summary In a double blind study 8 patients with uncomplicated essential hypertension received in random order single oral doses of placebo and 10, 30 and 80 mg Ro 23-6152, a novel calcium entry blocker, on 4 different days. Patients were assessed 15 min before dosing and at several time intervals over the following 6 h.Ro 23-6152 30 and 80 mg induced a significant decrease (mean maximum 7 mmHg·l^–1·min^–1) in total peripheral resistance, while cardiac output, stroke volume and heart rate were slightly increased (mean maximum 0.5 l·min^–1, 10 ml, 5 beats·min^–1, respectively) but not significantly so. Systolic blood pressure decreased significantly (5 to 10 mm Hg) from 0.5 to 6 h after the 80 mg dose. After the 10 and 30 mg doses the decreases in systolic pressure were not significant. Diastolic blood pressure and mean arterial blood pressure were non-significantly decreased (mean maximum 7 mm Hg) after all doses. The PQ interval was also non-significantly increased by no more than 20 ms.It appears that the main hemodynamic effect of Ro 23-6152 in hypertensive patients is a decrease in peripheral resistance. The antihypertensive effect, at least in this short term study, was only modest, probably because the fall in peripheral resistance was partly compensated by an increase in cardiac output.     

The effect of diuretic therapy on adrenaline-induced hypokalaemia and hypomagnesaemia

Summary We have examined the interaction between the administration of bendrofluazide, frusemide, spironolactone, and placebo and increased plasma adrenaline concentrations in a double-blind, placebo-controlled, cross over study.We studied healthy subjects on the fourteenth day of each treatment period and after a two hour infusion of adrenaline (0.06 µg·kg^–1·min^–1 {0.33 nmol·kg^–1·min^–1}) we measured their heart rates, blood pressures, and plasma potassium and magnesium concentrations.There were no differences in heart rates or blood pressures for all four treatments. Baseline potassium concentrations were not significantly different compared to placebo, and plasma potassium fell during the period of the infusion on all study days. this fall was significantly greater on frusemide (0.5 mmol·l^–1) and bendrofluazide (0.4 mmol·l^–1) compared with both placebo and spironolactone.Baseline plasma magnesium concentration were not different and similar falls in plasma magnesium were seen on all four treatments during and after the adrenaline infusion.We conclude that chronic diuretic therapy with a thiazide diuretic or frusemide may increase the severity of hypokalaemia during short-term rises in plasma adrenaline. Pretreatment with spironolactone had no effect on adrenaline-induced hypokalaemia. None of the diuretics studied altered adrenaline-induced hypomagnesaemia.     

Renal effects of manidipine hydrochloride

Summary The renal effects of manidipine hydrochloride were investigated in ten hospitalised patients with mild-to-moderate essential hypertension. After a one-week placebo period, manidipine was given for 1 week in a dose rising from 5 mg to 10 mg or 20 mg daily to normalise the mean blood pressure measured after 2 h.Blood pressure had decreased from 171/101 to 147/86 mm Hg at the end of manidipine treatment. The pulse rate was unaltered. Renal vascular resistance decreased from 1.90 to 1.33 dyn · s · cm^–5/1.48 m² × 10⁴, and renal blood flow and glomerular filtration rate increased from 522 to 662 ml · min^–1 · 1.48 m^–2 and from 81 to 93 ml · min^–1 · 1.48 m^–2, respectively, in spite of a fall in renal perfusion pressure. Manidipine reduced the filtration fraction from 0.260 to 0.243, suggesting a preferential reduction in efferent arteriolar resistance. The fractional excretion of sodium and potassium did not change. Manidipine did not produce any significant alteration in plasma renin activity or in the plasma aldosterone concentration.The results indicate that manidipine has favourable renal effects and a concomitant hypotensive action in patients with mild-to-moderate essential hypertension.     

Pharmacokinetics of ciprofloxacin tablets in renal failure; influence of haemodialysis

Summary The pharmacokinetics of ciprofloxacin has been studied after a single oral dose of 500 mg given to 5 normal subjects (N) and to 15 patients grouped according to their residual renal creatinine clearance: Group I, 8–30 ml·min^–1, Group II, <8 ml·min^–1, and Group III, haemodialysed patients studied twice — during an interdialysis period (IIIa) and in a 4 h haemodialysis session (IIIb). Ciprofloxacin was assayed by reverse phase HPLC using a spectrofluorimetric detection. The peak plasma concentration (2–5 mg·l^–1) was reached within 2 h after drug administration. Apparent volume of distribution, 6.6 (N), 5.0 (I), 2.7 (II) and 4.2 (IIIa) l·kg^–1 and total plasma clearance, 770 (N), 440 (I), 378 (II) and 314 (IIIa) ml·min^–1 were decreased in relation to the degree of renal impairment. Mean plasma half-lives for patients in the 4 groups were 7.3 (N), 10.4 (I), 7.2 (II) and 9.3 (IIIa) h. In groups N, I and II, 40, 16 and 8% of the administered dose was eliminated through the kidney, with mean renal clearances of 305±63,61±21 and 21±3 ml·min^–1. A linear relationship was found between the renal clearance of ciprofloxacin and the glomerular filtration rate (r=0.75,n=15). Ciprofloxacin was partly removed by haemodialysis (IIIb): the dialyser extraction ratio was 23% and the dialysis clearance was 40 ml·min^–1.     

Pharmacokinetics of ranitidine in patients undergoing haemofiltration

Summary The pharmacokinetics of ranitidine was investigated in 11 patients with acute or end stage renal failure during haemofiltration. Each patient received 50 mg ranitidine i.v.The mean distribution and elimination half lives were 0.13 and 2.57 h, respectively. The total body clearance (CL) and volume of distribution (V_z) were 298 ml·min^–1 (5.19 ml·min^–1·kg^–1) and 1.081·kg^–1, respectively. About 17.1% of the administered dose was removed by haemofiltration (in approximately 201 filtrate). Five of the patients still had some urine output and they excreted 0.1 to 11.8% of the dose in urine in 24 h. The haemofiltration clearance was 66.9 ml·min^–1 at a filtrate flow rate of 86 ml·min^–1, corresponding to a mean sieving coefficient of 0.78 (n=6). As plasma concentrations were still in an effective range after haemofiltration, dose supplementation is not recommended.     

Magnesium pyridoxal 5-phosphate glutamate reduces hyperlipidaemia in patients with chronic renal insufficiency

Summary Chronic renal insufficiency is often accompanied by hyperlipidaemia and subsequent coronary heart disease.Two groups of 15 patients with serum creatinine >2 mg/100 ml and serum cholesterol >250 mg/100 ml were given 3×50 mg magnesium pyridoxal 5-phosphate glutamate (MPPG) or placebo for 12 weeks in a double-blind, randomised study.Total cholesterol in the MPPG group (282.4 mg·100 ml^–1) was lower than in the placebo group (354.3 mg·100 ml^–1) after 12 weeks of treatment. Triglycerides in the MPPG group were 265.1 mg·100 ml^–1 compared to 361.9 mg·100 ml^–1. After 12 weeks on MPPG the LDL/HDL ratio of 3.56 was lower than in the placebo group — 6.83. Side effects in the MPPG group were similar to those in the placebo group. Thus, MPPG was an effective antihyperlipidaemic agent in patients with renal insufficiency.     

Exercise haemodynamic effects of beta-blockade and intrinsic sympathomimetic activity

Summary Beta-adrenergic blockade with intrinsic sympathomimetic activity (ISA) causes less depression of resting and submaximal heart rate (HR) than non-ISA beta-blockers. The effects of these drugs on exercise haemodynamics have not been well studied. We evaluated effects of pindolol, propranolol and placebo during rest and steady-state exercise on cardiac output, oxygen consumption, calf blood flow, HR and blood pressure in 18 healthy subjects.Pindolol 5 mg and propranolol 80 mg given twice daily, reduced maximal exercise HR by 50 and 52 beats·min^–1 respectively, confirming similarity of beta₁-blockade. Resting cardiac output was unchanged in all three groups after one week of therapy.Cardiac output, measured during steady-state exercise decreased in the propranolol group (18.3 vs 15.6 l·min^–1) with no significant changes in pindolol (15.7 vs 16.0 l·min^–1) or placebo (18.6 vs 17.3 l·min^–1). The rise in cardiac output, from rest to exercise, was similarly attenuated by propranolol but not by pindolol or placebo. Exercise stroke volume increased 12% on pindolol (123–140 cc) and decreased 7% on propranolol (143–133 cc).Neither drug had a detrimental effect on exercise calf blood flow compared to placebo. Thus, unlike propranolol, pindolol with ISA, maintains a normal cardiac output during submaximal exercise.Presented in part at the National meeting of the American Federation for Clinical Research, Washington, D.C., May, 1985     

Efficacy of terfenadine in the treatment of common cold. A double-blind comparison with placebo

Summary We have assessed the effects of terfenadine on rhinitis symptoms associated with the common cold in 91 patients in a double-blind placebo-controlled study. The patients received three doses of either terfenadine 60 mg (n=44) or placebo (n=47) at about 12-h intervals, starting in most patients within 48 h from the onset of symptoms. Because of deviations from the protocol, 28 cases were classified as not eligible for efficacy evaluation, but were nevertheless analysed.Excellent/good or moderate efficacy was reported by 63% of eligible and 59% of all patients who received terfenadine (placebo 40% and 51% respectively,p=0.049 and 0.113 respectively). 68% of eligible and 52% of all patients indicated that they would take terfenadine again (placebo 23%, for bothp=0.002). Two h after tablet intake mean nasal airflow was increased by 11 l·min^–1, SD 8 (placebo –1 l·min^–1, SD 6,p=0.005). Symptoms were improved and rhinoscopy showed reduced swelling and redness of the mucosa and reduced nasal secretion and obstruction (basically unchanged in the placebo group).Therefore, terfenadine seems to act favourably on the acute rhinitis symptoms associated with the common cold. Since terfenadine is devoid of anticholinergic activity, nose symptoms during the initial stage of the common cold may be mediated to an important degree by histamine.     

Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II

Summary The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng · kg^–1 · min^–1 was given before (control) and 30 min after the oral administration either of IS or P.After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II.In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.     

Pharmacokinetics and pharmacodynamics of thiazinamium in asthmatic patients

Summary The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction.Disposition after i.v. administration was described by a clearance of 0.54 l·min^–1, central compartment volume of 14.8 l, distribution rate constant 0.092 min^–1, and an elimination rate constant of 0.0044 min^–1. The corresponding estimates after i.m. administration were 0.324 l·min^–1, 34.1 l, 0.035 min^–1, and 0.0018 min^–1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC₅₀ of 12.8 ng·ml^–1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng·ml^–1, and 9 min.Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats·min^–1, with an EC₅₀ of 176 ng·ml^–1 and an equilibration half-time of 1.3 min. After i.m. administration the corresponding values were 120 beats·min^–1, 250 ng·ml^–1, and 3 min.The optimal plasma concentration of thiazinamium was about 100 ng·ml^–1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats·min^–1.     

Systemic and renal haemodynamic effects of angiotensin converting enzyme inhibition by zabicipril in young and in old normal men

Summary Zabicipril is a recently introduced angiotensin converting enzyme (ACE) inhibitor, which has been observed in experimental animals to increase diuresis, natriuresis, glomerular filtration rate (GFR) and renal plasma flow (RPF). We have investigated the acute effects of zabicipril on systemic and renal haemodynamics in two groups of 8 sodium-replete normal men, aged 23 to 30 y and 65 to 74 y. Zabicipril 0.5 mg, 1 mg or 2.5 mg and a placebo were administered orally, at one week intervals, in a random order and in a double blind fashion. Haemodynamic measurements were performed at base line and every hour for 4 hours after intake of drug or placebo. Cardiac output (Q) was measured by Doppler echography, and RPF and GFR by the constant infusion technique using I¹²³ iodohippurate and Cr⁵¹ EDTA, respectively.In the young men zabicipril did not affect Q, heart rate (HR), systemic arterial pressure (AP) or GFR, but it did increase RPF at the 4th hour after the highest dose (from 540 to 653 ml · min^–1 · m^–2). In the old men zabicipril had similar actions, but the effect of the highest dose on RPF (from 355 to 415 ml · min^–1 · m^–2) was less marked than in the young men. In the young and old men the inhibition of ACE peaked at about of 90% or more from the 2th to the 4th hour after the highest dose of zabicipril.We conclude that, in normal men, zabicipril increases the renal fraction of cardiac output in the absence of a concomitant change in systemic haemodynamics. This specific effect of zabicipril on the kidney may be less important with advancing age.     

OACE inhibition does not interfere with acute extrarenal or renal potassium disposal in chronic renal failure

The influence of angiotensin converting enzyme (ACE) inhibition on acute extrarenal and renal potassium elimination in stable chronic renal failure has been examined in 10 male patients median age 44 y; mean CL_CR 42 ml·min^–1·1.73 m^–2. In a double blind, placebo-controlled cross-over study, K⁺ 0.3 or 0.4 mmol·kg^–1 body weight was infused IV on two occasions while the patients also received an infusion either of placebo or 0.5 mg of the ACE inhibitor perindoprilat in random order. Plasma K⁺ levels and urinary K⁺ excretion were measured at regular intervals. During the study patients adhered to an isocaloric diet providing a standardised daily intake of potassium and sodium (50 mmol K⁺ and 40 mmol Na⁺).The median rise in plasma K⁺ was not significantly different after placebo ( K 0.66 mmol·1^–1) compared with to the infusion of perindoprilat ( K 0.66 mmol·1^–1). The median baseline urinary K⁺ excretion rate was 6.5 mmol·3 h^–1 before the placebo infusion and 5.9 mmol·3 h^–1 before infusion of perindoprilat. During the potassium load, the urinary excretion rate rose to 16.1 mmol·3 h^–1 (after placebo) and 15.1 mmol·3 h^–1 after perindoprilat in the first 3 h, and it returned almost to the baseline value within the next 3 h (5.6 mmol·3 h^–1 after placebo and 5.7 mmol·3 h^–1 after perindoprilat); the differences were not statistically significant.With perindoprilat a decrease in mean arterial blood pressure and ACE activity, an increase in renin plasma activity and a decrease in aldosterone concentrations were observed compared to the placebo infusion. There was no significant differences plasma in adrenaline or insulin levels after either infusion.Thus, ACE inhibition did not interfere either with the extrarenal or the renal disposal of an acute potassium load in patients with chronic renal failure.