Comparison of the antianginal efficacy of four calcium antagonists and propranolol in stable angina pectoris.

The antianginal effects of propranolol 160 mg/day, diltiazem 240 mg/day, nicardipine 80 mg/day, nifedipine 40 to 80 mg/day and verapamil 320 mg/day were compared in 12 patients with chronic stable angina pectoris using a symptom-limited exercise test. Compared to placebo propranolol and calcium antagonists similarly reduced (p less than 0.001) the frequency of antianginal attacks and nitroglycerin consumption, and increased exercise tolerance and time to greater than or equal to 1 mm S-T segment depression. After propranolol the pressure-rate product at submaximal and maximal exercise was significantly decreased. The calcium antagonists produced a significant reduction in the submaximal pressure-rate product, but no significant change in the peak pressure-rate product. Maximum ST depression was significantly lower after propranolol and was unchanged after the calcium antagonists. None of the drugs caused significant adverse effects. The results indicate that in patients with stable effort angina pectoris, diltiazem, nicardipine, nifedipine and verapamil were as effective as propranolol in improving exercise tolerance and time to ischaemia, and they did not alter the peak pressure-rate product. Different antianginal mechanisms may be operative for the various calcium antagonists.

Ibopamine kinetics after single and multiple dosing in patients with congestive heart failure.

The pharmacokinetics of ibopamine after single and multiple dosing was studied in 20 patients with congestive heart failure (CHF) of NYHA functional class II. Ibopamine 100 mg was given 3 times a day for 7 days in 6 patients and for 30 days in the other 14 patients. Plasma pharmacokinetics of total (mainly conjugated) and free epinine was studied after the first dose and on the 3rd, 7th and 30th days of treatment. The urinary recoveries of total epinine, HVA and DOPAC were measured in 5 patients for 24 h after ibopamine ingestion on the 1st and 30th days. Plasma pharmacokinetics of ibopamine did not vary during the repeated administration of the drug. In the course of the treatment, total epinine elimination t1/2 showed no significant variations. The build-up of Cmax, Cmin and AUC of total epinine observed after multiple dosing was as expected on the basis of the interval adopted between the doses of ibopamine and of the elimination t1/2 of total epinine. Pharmacokinetic parameters of free epinine did not show significant variations during the course of the treatment. The amounts of HVA and DOPAC recovered in urine on the 1st and 30th days of treatment were similar while the amount of total epinine was greater on the 30th day, the increment mainly reflecting a partial carry over of the less rapidly excreted conjugated epinine from the last previous doses. The results obtained for free epinine plasma levels and for the urinary recoveries of ibopamine metabolites thus indicated that no saturation of the enzymes involved in ibopamine metabolism occurred.

Ibopamine kinetics after a single oral dose in patients with congestive heart failure.

The kinetics of ibopamine, the 3,4-diisobutyryl ester of N-methyldopamine (epinine), was assessed in 27 patients with congestive heart failure (CHF) and 8 healthy normal subjects (NS). Nine patients were in functional class IV according to the NYHA definition, 9 in class III and 9 in class II. Ibopamine was administered at a single oral dose of 100 mg. Epinine, both free and total (mainly conjugated), plasma concentrations and urinary recoveries of total epinine, HVA and DOPAC were studied. The results showed that ibopamine kinetics is not substantially different in CHF patients and in NS. In both groups the absorption of the drug was equally prompt and elevated. Mean Cmax, tmax and AUC infinity values of total epinine in CHF patients did not differ significantly from those in NS. In CHF patients t 1/2 of total epinine was significantly higher than in NS (4.1 +/- 0.2 h vs 3.1 +/- 0.2 h, mean +/- SE). Mean Cmax, tmax, AUCt and MRT values of free epinine in CHF patients were not significantly different from those in NS. The urinary recovery of the 3 metabolites considered together was comparable in CHF patients and in NS. The mean +/- SE total urinary recoveries in the 24 h after dosing, expressed as percentages of the administered dose, were 60 +/- 3 in CHF patients and 69 +/- 4 in NS. Conjugated epinine in urine was found to be constituted by 3-O-sulfate (84%) and 4-O-sulfate (16%).