Four hundred and fifty patients aged 75 years or older were followed up after discharge from an accident and emergency department. Forty-three per cent of all patients experienced some loss of functional independence. A small number, 5.6%, were readmitted to hospital within 14 days. This group were significantly less able to perform certain activities of daily living than those not readmitted. Attention to functional assessment by casualty staff may help to prevent readmission to hospital of this frail elderly group of patients.

Eight healthy young and nine healthy elderly volunteers received 10 mg morphine sulphate as an intravenous infusion, an oral solution and a slow-release tablet (MST Continus, Napp Laboratories) on three separate occasions. Pharmacokinetic profiles of morphine base were measured over a 24-h period using 13 sampling times. The elderly group showed decreased morphine clearance with a trend to a smaller volume of distribution. They achieved higher maximum plasma concentrations (Cmax) after both oral formulations and had larger areas under the plasma concentration-time curves. The times to reach maximum concentrations were the same in both groups for all formulations.

The hepatic clearance of many drugs is reduced in the elderly. Contrary to previously held views we suggest the following: 1. Specific activities of several cytochrome P-450 Phase I enzymes are not reduced with age per se in primate and man, nor is enzyme affinity for substrate changed. 2. An important contribution to the reduced hepatic elimination is made by reduction in liver size and blood flow with advancing age. 3. Major changes in liver drug metabolism may occur in frail old people. Future studies of hepatic drug metabolism and ageing must closely define the subject groups under study.

The hepatic extraction ratio and clearance of indocyanine green (ICG) were determined and used to derive apparent liver blood flow in nine subjects between the ages of 22 and 83 years. There was no correlation between the hepatic extraction ratio of ICG and age (rs = -0.435, NS). There was a significant negative correlation between both ICG clearance and age (rs = -0.710, P < 0.05) and apparent liver blood flow and age (rs = -0.750, P < 0.05). These results validate the comparison of liver blood flow values derived from ICG clearance in humans over a wide age range and confirm that liver blood flow does fall with age.

Although the clearance of many oxidized drugs falls with age, a corresponding fall in the maximal activities of drug metabolizing enzymes has not been noted. The possibility of a fall in enzyme affinity for substrate with age, which could account for the observed changes, has not previously been investigated in human liver. We have studied the kinetics of the microsomal mono-oxygenase 7-ethoxycoumarin-O-de-ethylase in 17 human liver biopsy specimens. No correlation was observed between age and microsomal protein recovery, maximal enzyme activity or apparent enzyme affinity. Since microsomal mono-oxygenase activities and affinities appear not to change in human liver, other factors such as a fall in liver volume or blood flow must be responsible for the decline in clearance of many oxidized drugs which occurs with ageing.