Observations on three dosage forms of pindolol

Cardiac effects of single doses of conventional oral pindolol, sustained-released oral pindolol, and intravenous pindolol were studied in healthy male volunteers, aged 21 to 27 years, weighing 70.8 to 92.1 kg. The studies were designed to evaluate the oral dose-response curve of pindolol, to assess the partial agonist activity of pindolol, to determine the systemic bioavailability of oral pindolol, and to compare the systemic bioavailability, potency, and duration of action of comparable beta-adrenergic-blocking doses of pindolol and propranolol. In study A, eight subjects randomly received at weekly intervals oral pindolol, 5, 10, 15, and 20 mg (2 × 10 mg), and sustained-release pindolol, 20 and 30 mg. Supine resting (RHR), standing (SHR), and exercise heart rates (EHR) were recorded at 0 hours (before dose) and at 2, 8, and 24 hours after dose. Control RHR averaged 57.0, SHR 98.2, and EHR 162.8 bpm. None of the doses produced any significant reduction in RHR or SHR. Average EHR at 2 hours was 122.3 bpm, with no significant difference between the six doses. At 8 and 24 hours, the larger doses produced greater reductions in EHR. At 24 hours, the 5 mg dose had no residual effect, whereas other doses had intermediate residual blockade with the maximum of 50% recorded after the sustained-release 30 mg dose. The effects of the 20 mg doses were not significantly different. In study B, eight subjects randomly received at weekly intervals oral pindolol, 5 mg; intravenous pindolol, 0.045 mg/kg; oral propranolol, 80 mg; and intravenous propranolol, 0.3 mg/kg. Intravenous pindolol (0.2 mg/ml) and intravenous propranolol (1 mg/ml) were administered by Harvard pump at 1 mg/min. RHR, SHR, and EHR were measured at 0 hours (before dose) and 0.5, 1, 2, 4, 6, 8, and 24 hours after dose. No dose had any significant effect on RHR. Pindolol doses had no effect on SHR but propranolol orally and intravenously reduced SHR to about 82 bpm; the difference between the drugs was significant ( p