The lack of effect of aerobic exercise training on propranolol pharmacokinetics in young and elderly adults

The effects of exercise training on the pharmacokinetics of orally administered propranolol were studied in young and elderly healthy volunteers. Twenty-three young (30 +/- 5 years of age) and 20 elderly (67 +/- 5 years of age) adults were randomly assigned to endurance training (N = 12 young subjects, 10 elderly subjects) or nonexercising control (N = 11 young subjects, 10 elderly subjects) groups. Training consisted of treadmill walking, stair climbing, or both three times per week for 40 minutes at 70-85% of maximal heart rate reserve for 16 weeks. Resting plasma propranolol concentrations after a single dose of 80 mg of oral propranolol were measured by high performance liquid chromatography with fluorescence detection, and estimated hepatic blood flow measured was measured using indocyanine green during supine test. Aerobic training increased maximal oxygen uptake (VO2 max) by 13% and 14% in the exercising young and elderly groups, respectively. There was no change in VO2 max in either control group. Adjusted mean estimated hepatic blood flow after exercise corrected for body weight for the young subjects who did not exercise (15.6 mL/min/Kg) and those who did (18.2 mL/min/Kg) groups were of borderline significance. No statistical differences were detected in the experimental propranolol pharmacokinetic parameters (maximal concentration, time of maximal concentration, terminal half-life, area under the curve, and protein binding) or derived pharmacokinetic parameters (intrinsic clearance, bioavailability, clearance, and volume of distribution). These results provide evidence that changes in aerobic fitness do not produce corresponding changes in propranolol pharmacokinetics in young or elderly adults.
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