The effect of ageing on the hepatic clearance of propranolol.

Abstract

1. Plasma propranolol concentrations were measured in healthy old and young subjects following single oral doses of 40 mg, single i.v. infusions of 0.15 mg kg‐1 and after nine 40 mg oral doses given four times daily. 2. In each of the three studies, the elderly had higher plasma propranolol concentrations than the young despite having similar apparent volumes of distribution. 3. The terminal half‐life of propranolol was similar in the two groups after oral propranolol but significantly shorter in the young after intravenous dosing (P less than 0.05). 4. The bioavailability assessed from the concentration‐time curves after i.v. and oral dosing was greater in the elderly (P less than 0.05). 5. The differences between peak concentrations observed in old and young subjects after single oral doses were maintained during chronic therapy and there was a correlation between the individual values obtained on multiple therapy with that after a single dose (P less than 0.05). 6. Ageing appears to affect the pharmacokinetics of propranolol in two ways. Firstly, distribution to the tissues appears to be slowed. Secondly, the increased bioavailability following oral administration suggests diminished intrinsic clearance by metabolism.

Pharmacokinetic and pharmacodynamic characteristics of trazodone in the elderly.

“…Such a reduction has been clearly demonstrated in animals (Kato & Tanaka, 1968) and studies in man have confirmed a reduction in liver size and the number of functioning liver cells with increasing age (Sato et 1970). In the elderly, the decreased plasma clearance of antipyrine (O'Malley et al, 1979) and propranolol (Castleden & George, 1979), have been attributed to a lower rate of metabolism. They all share, with trazodone, a common route of elimination; hydroxylation.…”

Prazosin disposition in young and elderly subjects.

“…Pharmacokinetic studies in the elderly have been performed using intravenous administration with only a few drugs including antipyrine (O'Malley etal., 1971) phenytoin (Hayes, Langman & Short, 1975) diazepam (Klotz et al, 1975), chlordiazepoxide (Roberts et al, 1978), propranolol (Castleden & George, 1979), chlormethiazole and lignocaine (Triggs, 1979).…”

The influence of age, smoking and hyperthyroidism on plasma propranolol steady state concentration.

“…phenytoin (Houghton, Richens & Leighton, 1975), imipramine and amitriptyline (Nies et al, 1977). This effect of age on plasma drug steady state concentration will be most obvious with drugs such as propranolol which are extensively metabolised by the liver and there is evidence (Castleden & George, 1979) that the elimination of propranolol is reduced in elderly subjects. The hepatic metabolism of some drugs may be increased in hyperthyroidism (Eichelbaum, 1976) and it is also known that smoking, probably through hepatic enzyme induction (Vestel et al, 1975) increases the rate of elimination of certain drugs and may thus be a complicating factor when assessing the influence of age on drug handling.…”

“…These results suggest that the younger hyperthyroid patient who smokes may achieve only a minor degree of /3-adrenoceptor blockade on conventional dosage of propranolol. The findings of higher concentrations of propranolol has lead Castleden & George (1979) to suggest that propranolol dosage should be reduced in the elderly. We feel however, that this may not be necessary.…”