1 Parallel human and rat studies were carried out to confirm the previous suggestion of an increased sensitivity to warfarin in old age. 2 The anticoagulant response to warfarin was found to be greater in the elderly groups despite, in the case of the patient study, the elderly subjects being given a smaller weight‐related dose. 3 At the same plasma warfarin concentrations there was greater inhibition of vitamin K‐dependent clotting factor synthesis in the elderly. There was no difference in the rate of clotting factor degradation in the two age groups. 4 There was no appreciable difference in warfarin pharmacokinetics (plasma half‐life, apparent volume of distribution, plasma clearance, plasma protein binding or plasma warfarin alcohol levels) in the two age groups. 5 There appeared to be no major age‐ related differences in warfarin pharmacokinetics and the increased effect of warfarin in the elderly seemed to result from an increased intrinsic sensitivity to warfarin.

S‐(‐)‐Warfarin was found to be a more potent anticoagulant than R‐(+)‐warfarin in man. However, S‐warfarin was cleared more rapidly from the plasma; respective mean plasma half‐lives (from four subjects) for R and S‐warfarin were 45ṁ4 and 33ṁ0h. Unlike the assay of Lewis, Ilnicki & Carlstrom (1970), the assay of Corn & Berberich (1967) for measuring plasma warfarin gave spuriously long half‐life values, particularly with R‐warfarin. The apparent volumes of distribution of the enantiomers were not significantly different. A major plasma metabolite detected was warfarin alcohol1, which was seen in much greater quantities after giving R‐warfarin than after S‐warfarin. The corresponding diastereoisomer, warfarin alcohol2, was seen in trace amounts after S‐warfarin only.

1We examined the case notes of 82 psychiatric out-patients (aged 21-84 years) receiving lithium prophylaxis and with steady-state plasma lithium levels. 2 The mean weight-related daily dose of lithium prescribed decreased by about 50% between the third and eighth decades. 3 The corresponding steady-state plasma lithium levels showed a less marked tendency to decrease, this only being seen in the seventh and eighth decades. 4 In patients aged 50 years or over the daily lithium dose required to give a plasma level of 1 mmol 1-1 (0.50 mmol kg-') was significantly lower than that (0.65 mmol kg-') in patients aged under 50 years (P < 0.005, Student's t-test). In patients aged 70-79 years this dose was 31 % lower than in patients under 50 years. However, interindividual variation was great and it was estimated that age only contributed about 14% to the total interpatient variation. 5Of the 36 patients under 50 years of age, 42% had minor lithium side-effects and 17% were not optimally controlled with lithium. The corresponding figures for the 46 'older' patients were 46% and 28%. 6 Generally the 50% dosage reduction seemed necessary to compensate for an age-related decrease in lithium excretion and to reduce lithium side effects to a level comparable to that acceptable in younger patients.

SynopsisOne hundred and sixty-six unipolar and bipolar out-patients (21–78 years) on long-term lithium treatment were studied on a prospective basis. Although there was a possible tendency for manic attacks to increase in prevalence and severity with age, it was difficult to demonstrate a general age-related decline in lithium efficacy. There was a tendency for the prevalence and severity of fine hand tremor to increase with age. This was not seen with polydipsia/polyuria, the other typical lithium side-effect.