Using recently developed radioimmunoassay, the fact that the incidence of digitalis intoxication clinically increased with age in the adult population prompted us to measure serum digitoxin concentrations in patients with oral maintenance doses of digitoxin, and to investigate their clinical significance by a comparative study between the elderly (sixty or more years) and the younger (below sixty years) patients.
The results were as the following.
1. While the average serum concentration for the nontoxic group was 18.4ng/ml, that for the toxic group was as high as 35.5ng/ml. The difference was statistically significant. (P<0.0001)
2. The comparison of clinical data between the toxic group and the nontoxic was performed. The cardiothoracic ratio, GOT and GPT showed a significant difference between the two groups.
3. The serum concentrations significantly increased in proportion to the increase of the maintenance doses of digitoxin, and the regression equation was calculated as: y=194x+4.87. All the cases with serum concentrations above 35ng/ml manifested toxicity, while none of the cases with serum concentrations below 24.5ng/ml were toxic. An overlapping existed in the range between 24.5 and 35.0ng/ml.
4. In each group of three different maintenance doses (0.05mg/day, 0.07-0.08mg/day, 0.1mg/day), the average serum concentration was higher in the elderly than in the younger, and the differences were statistically significant.
The regression equations were calculated as: y=231x+3.91 (in the elderly group), y=148x+5.39 (in the younger).
While only 3 cases of 53 patients, that is 5.6% had manifestations of toxicity among the younger group, 21 cases of 62, or about 34% of the patients had manifestations of toxicity among the elderly.
5. The body-weight and the cardiothoracic ratio were not significantly different between the two groups. Among the blood chemistry examinations, total serum protein was significantly different, but no significant differences were noted in BUN, creatinine, sodium and potassium. Thus, renal function as revealed by BUN and creatinine was not thought to be different between the two groups. However, it seems that as 24-hour endogenous serum creatinine clearances decreases, serum digitoxin concentration and hence the incidence of toxicity tend to increase.
However, taking into consideration the fact that the more polar metabolites of digitoxin are mainly excreted by the urinary route, it is appropriate that the diminution of GFR by aging is counted as one of the main factors contributing to the high serum digitoxin concentration in the elderly.
Furthermore, various factors such as the impairment of the activity of drug metabolising enzymes were discussed in this pages. Accordingly, cautious consideration of dosage and careful observation of the clinical condition are required in treating the elderly patients.
It is very useful to dertermine the serum digitalis concentrations frequently in the clinical course for the early detection of digitalis intoxication.
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