Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.

Abstract

1 Pharmacokinetics of pindolol were studied in normal subjects given 5, 10 and 20 mg orally and 3 mg i.v. Plasma half time was 2.9 +/‐ 0.3 (s.e. mean) h for both routes; peak drug levels occurred 1–2 h after ingestion and bioavailability was 53%. Plasma protein binding was 38% and was independent of plasma concentration; the drug was not concentrated in the red cell. 2 Work‐heart rate regression lines were calculated from resting heart rate and three grades of 'steady‐state' exercise standardized for the maximum work capacity (Wmax) of each subject. The equation was characterized by slope and HR50 (calculated heart rate at 0.5 Wmax). 3 After giving 5 mg i.v. pindolol to produce maximum cardiac beta‐adrenoceptor blockade there were differences in inhibition of resting heart rate, slope, HR50 and maximum heart rate suggesting differences in sympathetic components. However, estimates of the degree of inhibition were closely similar for each variable when determined before and after atropinization indicating that the accuracy of estimation was independent of the level of vagal activity. 4 After oral pindolol peak inhibition of resting heart rate, slope and HR50 coincided with peak plasma concentration. Peak reduction of resting heart rate was greatest at the lowest dose, but inhibition of slope and HR50 were similar at all doses. 5 The different heart rate parameters recovered at different rates. After 24 h slope had returned to control, and the residual inhibition of HR50 reflected residual beta‐ adrenoceptor blockade of resting heart rate, as demonstrated by a shift in isoprenaline‐heart rate relationship. 6 Inhibition of HR50 and other exercise parameters were 20% less in the concentration range 5–20 ng/ml than peak inhibition obtained in the range 21–160 ng/ml. The higher potency of pindolol compared with propranolol can be accounted for by the difference in protein binding.

Absorption and excretion of rapid and slow release oxprenolol and their effects on heart rate and blood pressure during exercise.

“…The apparent rate of absorption of oxprenolol for both formulations was calculated as described for other beta blocking drugs (Johansson, Regardh & Sjogren, 1971;Regardh, Johnsson, Jordo & Solvell, 1975 (Jennings, Bobik, Fagan & Korner, 1979). For the present investigation we compared the effects of RR and SR oxprenolol on the 'steady-state' response to severe exercise instead of on the response to several grades of exercise as in the previous study (Jennings et al, 1979).…”

“…For the present investigation we compared the effects of RR and SR oxprenolol on the 'steady-state' response to severe exercise instead of on the response to several grades of exercise as in the previous study (Jennings et al, 1979). Each subject exercised for 4 min at 75% of Wmax performed during 'sprint' exercise.…”

“…Maximum heart rates during the last min of the 4 min exercise (1-EHRt/EHRC) x 100 where EHRc is the control exercise heart rate determined prior to administering oxprenolol and EHRt is the heart rate during exercise at time t after administering oxprenolol. Systolic blood pressure measurements were obtained with the subjects seated on the bicycle ergometer at rest and during the last min of the exercise protocol as described previously (Jennings et al, 1979).…”

Exercise Training Increases Basal Nitric Oxide Production From the Forearm in Hypercholesterolemic Patients

“…26 This test consisted of 1-minute periods of bicycle exercise commencing at zero workload and increasing by 20 watts each minute until any further increase in workload was prevented by fatigue. The criteria for establishment of VO 2 max included a plateau in the oxygen consumption with increasing work rate, a respiratory exchange ratio Ͼ1.1, and failure to maintain the required workrate despite encouragement.…”

Increases in plasma beta‐endorphin concentrations during exercise do not contribute to increases in heart rate following autonomic blockade in man.

“…All were non-smokers and none were heavy drinkers. Each subject's maximum work capacity (Wmax) and maximum Correspondence: Dr J. Chin, Alfred and Baker Medical Unit,Baker Medical Research Institute,Commercial Road,Prahran,3181 Victoria, Australia *Present address: Baker Medical Research Unit, Commercial Road, Prahran, 3181 Victoria, Australia oxygen consumption (V02 max) was determined using a graded sprint test on a cycle ergometer (Ergoline 900) which involved starting at 0 watts and increasing by 20 watts each minute until further increase in workload (watts) was prevented by fatigue (Jennings et al, 1979 (Jennings et al, 1979). Four subjects were randomly allocated to receive naloxone (10 mg over 10 min) during the first session while the other four received naloxone during the second session.…”