Twenty‐eight elderly volunteers of the 65+ age group and 28 control subjects of the 20–40 age group each received a single oral dose (1 gm) of acetaminophen in powder form. The plasma level of acetaminophen was measured over 6 hours. Plasma half‐life, clearance and relative volume of distribution of the drug were calculated. Within each age group there was a wide (threefold) range of plasma half‐life and clearance rate, with a great deal of overlap between the two groups. However, for the elderly, the group mean half‐life of acetaminophen was 2.17 hours, significantly longer than for the young (1.75 hours). The clearance rate in the elderly was significantly slower than in the young (.254 and .340 L/kg/hour respectively). There was no age‐related difference in volume of distribution of the drug by any measure, and no significant influence of sex.

1. The effects of single oral doses of propranolol, practolol and a new cardioselective beta-adrenoceptor blocking drug, metoprolol, on exercise-induced tachycardia in relation to plasma levels were studied in six normal volunteers. 2. Exercise undertaken on treadmill was submaximal which, under control conditions, increased the heart rate from 74-3 (s.e.m. = 6-8) to 153-8 (s.e.m. = 9.8) beats/min. 3. Plasma concentrations of propranolol and practolol were assayed fluorometrically and of metoprolol by electron-capture gas liquid chromatography, the details of which are described. 4. Between 1-5 and 2 h after drug ingestion 80 mg of propranolol associated with plasma level of 50-60 ng/ml (half-life 2-75 h), reduced the exercise-induced tachycardia by 27%, 250 mg of practolol with plasma levels of 1050-1100 ng/ml reduced it by 28% and 100 mg of metoprolol with plasma concentrations of 140-150 ng/ml (half-life 1-7 h), reduced it by 30%. 5. The resting heart rates were reduced significantly by propranolol and metoprolol but not by practolol. 6. Metoprolol is a potent short-acting beta-adrenoceptor antagonist; its advantages as a cardioselective agent over practolol in therapeutic use are discussed.

The bioavailability of metoprolol was studied in eight healthy young and seven healthy elderly volunteers. Large interindividual differences in the bioavailability of metoprolol were observed in both groups. However, there was no significant difference in AUC, peak plasma concentration or elimination half-life between young and elderly, but time to peak concentration was significantly longer in the elderly. Pretreatment with metoclopramide had no effect on AUC but caused significant increases in peak concentration and decreases in time to peak concentration in both groups. Probanthine pretreatment (only to the young) resulted in a significant decrease in peak concentration of metoprolol and a significant increase in time to peak concentration but had no effect on the AUC. These results suggest that alterations in gastric emptying and gut motility due to ageing or other drugs have no effect on the overall availability of metoprolol to the systemic circulation but may have significant effects on the time to peak plasma concentration and peak concentration achieved after a single oral dose.