1 Comparison of phenytoin clearance showed a marked increase in people over 65 years of age compared with people under 45 years of age. 2 This difference was apparent if phenytoin was given orally or intravenously. 3 Phenytoin clearance correlated inversely with phenytoin binding and plasma albumin, both of which were found to be reduced in the elderly.

1 A decrease was found in the binding capacity of elderly people for warfarin. 2 The decrease in binding correlated with a fall in plasma albumin concentrations. 3 No changes in the association constant were observed.

The dermal toxicity of phenol: an investigation of the most effective first-aid measures. The percutaneous toxicity of phenol in the Alderley Park (Wistar derived specific pathogen free) rat was determined and was shown to be increased by the diluents water, methylated spirit or olive oil. The toxicity was related to the degree of dermal damage in one minute, and this was greatest when the phenol was diluted 1 : I or 2: 1. First-aid procedures were investigated, and the following is recommended: 1. Remove all clothing as quickly as possible. First-aiders must take care to avoid contaminating themselves. Percutaneous toxicity of phenol This was examined by an occlusive technique in which a single application was made to the shorn backs of groups of five rats and the treated areas were covered with polythene held in place by waterproof adhesive dressing 155

SUMMARYComparison by equilibrium dialysis of plasma protein binding sites for carbenoxolone in people under 40 years of age and in people over 65 years of age showed that the number of binding sites was reduced in the elderly and that this fall was associated with a reduction in plasma albumin levels. Although carbenoxolone has some aldosterone-like effects, these properties could not be shown to be due to displacement of aldosterone from its protein binding sites by competitive protein binding of carbenoxolone. Single doses of carbenoxolone were found to be removed considerably more slowly from the plasma of elderly individuals than from the young. The results of these three series of experiments suggest that the side-effects of carbenoxolone in the elderly may in part be caused by reduced protein binding, leaving more free drug in the active unbound form, and in part by reduced hepatic clearance mechanisms.