Effectiveness of ibopamine in the management of ascitic liver cirrhosis--a controlled study v placebo and frusemide.

1 Thirty in-patients of both sexes suffering from ascitic liver cirrhosis were divided into three groups treated with (a) a placebo, (b) ibopamine (SB 7505, a new oral dopaminergic drug) and (c) frusemide, for 10 days. 2 Body weight decreased with both frusemide and ibopamine, diuresis and urinary excretion of Na+ and Cl- increased with both drugs; whereas urinary excretion of K+ increased only with frusemide. 3 An important difference between the frusemide and ibopamine treatment was encountered in creatinine clearance, which increased only with ibopamine, and in blood uric acid which increased only with frusemide. 4 The antidiuretic hormone (ADH) in the plasma of cirrhotic patients was lower than the sensitivity limit of the radioimmunoassay method, whereas in a group of healthy subjects it could be clearly measured. 5 The treatments did not affect systolic or diastolic blood pressure, heart rate, or a series of haematochemical parameters. 6 The increase in diuresis and creatinine clearance and the very good tolerability encountered with ibopamine highlight this new oral dopamine agonist as a useful drug in the management of liver cirrhosis.

Renal effect of SB 7505: a double-blind study.

Two groups of 20 patients with no evidence of cardiovascular, hepatic, renal or gastrointestinal failure were treated orally for five days with placebo or SB 7505 100 mg/day. No change was observed in heart rate or blood pressure. Urine output, the excretion of Na, K and Cl, and creatinine clearance were significantly increased.

Clinical tolerability of ibopamine hydrochloride (SB 7505).

The clinical tolerance of ibopamine hydrochloride (Sb 7505) was investigated in 12 volunteers. The drug was administered on alternate days (2nd, 4th, 6th, 8th, 10th, 12th), starting at 100 mg and increasing by 50 mg each time to reach 350 mg on the 12th day. On the other days (1st, 3rd, 5th, 7th, 9th, 11th and 13th) a placebo was given. Diuresis increased progressively with the dose, reaching a maximum increase of 88% after the last dose, and showing a small residual effect on each subsequent placebo day. Body weight showed a marginal change and decreased by 2% in the last two days of treatment. Heart rate, systolic, diastolic and mean blood pressure showed only marginal fluctuations of about 7% around the mean values, which were of little statistical and of no clinical significance. Haematological and biochemical parameters were not affected. No side effect was noticed. The dose of 350 mg may probably be increased without leading to side effects.

[Effects of dopamine, noradrenaline and isoproterenol on pulmonary circulation in anesthetized dogs]. / Effetti della dopamina, della noradrenalina e dell'isoproterenolo sul circolo polmonare di cani anestetizzati.

Experiments were performed on 19 anaesthetized open-chest dog instrumented with polyethylene catheters inserted: into the aorta, in pulmonary artery and in left atrium and with an electromagnetic flow-transducer placed around the ascending aorta in order to record : systemic arterial and pulmonary pressures, mean left auricular pressure and phasic aortic flow. Heart rate, stroke volume, total systemic and pulmonary resistance, cardiac work were moreover calculated. Each dog was given intravenously by slow infusione : Dopamine (micrograms 5--10--20/kg/min/ 5 min), Isoproterenol (microgram 0.125--0.25--0.5/kg/min/5 min) and Norepinephrine (microgram 0.25--0.5--1 /kg/min/5 min). Results obtained on systemic hemodynamics agree with those reported by many other investigators. On pulmonary circulation : Isoproterenol, at the tested doses, elicited vasodilator effects, Norepinephrine increased total pulmonary resistance but not pulmonary vascular resistance, while Dopamine did not modify or slightly reduced vascular pulmonary tone.

Acute clinical tolerance of creatinol O-phosphate.

Acute clinical tolerance to N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was investigated in volunteer human subjects without heart or renal disease and without other serious illness. COP was administered i.v. at three different dosages, 1020 mg (group A), 2040 mg (group B) and 3060 mg (group C), in comparison with a placebo (group D). Arterial pressure, heart rate, ECG pattern and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups B and C. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule and the increase in diuresis from a simple osmotic process required to dilute the phosphate in the tubular fluid. All these alterations were statistically significant and dose-related with COP and had been expected. COP proved to be a very well tolerated drug without any evident side effect.