The relationship between phenazone (antipyrine) metabolite formation and theophylline metabolism in healthy and frail elderly women.

The influence of aging on the metabolism of phenazone (antipyrine), and the relationship between the formation of 3 phenazone metabolites and the metabolic clearance of theophylline in healthy and frail elderly women, were examined. Whereas the elimination half-life did not change, clearance of phenazone decreased by about 50% with age in healthy women receiving phenazone without theophylline. However, the summation of the urinary recovery of phenazone and the measured metabolites, expressed as percentage of the phenazone dose, was lower in the healthy elderly (37 +/- 9% vs 74 +/- 15%). In both healthy and frail females the clearance of formation of 4-hydroxy-phenazone and the metabolic clearance of theophylline correlated strongly (r = 0.93 and 0.90, respectively). In non-healthy elderly females, strong correlations were also observed between the other metabolic pathways of phenazone and the metabolic clearance of theophylline. Coadministration of theophylline in the elderly increased the percentage of the phenazone dose excreted as the measured metabolites. A considerably higher interindividual variability in the disposition of phenazone and theophylline was observed in the frail elderly women. This high degree of variability in drug metabolism may be one of the explanations for the problems often occurring after drug prescription in the elderly.

Inappropriate medication is a major cause of adverse drug reactions in elderly patients.

To determine the extent to which adverse drug reactions (ADRs) in elderly patients admitted to hospital are due to inappropriate prescribing, we examined 416 successive admissions of elderly patients to a teaching hospital. Interacting drug combinations and drugs with relative contra-indications (CIs) were common, but not as important in producing ADRs as drugs with absolute CIs or unnecessary drugs. Forty-eight patients (11.5% of admissions) were taking a total of 51 drugs with absolute CIs (3.8% of prescriptions). One hundred and seventy-five drugs were discontinued on or shortly after admission in 113 (27%) patients because they were deemed to be unnecessary. One hundred and three patients (27.0% of those on medication) experienced 151 ADRs of which 75 (49.7%) were due to drugs with absolute CIs and/or that were unnecessary, a significantly higher rate of ADRs (p less than 0.001) than observed for all prescriptions. Of 26 (6.3%) admissions attributed to ADRs, 13 (50%) were due to inappropriate prescriptions. The admission rate per prescription was significantly higher (p less than 0.001) for inappropriate than for appropriate drugs. We conclude that much drug-related morbidity in the elderly population may be avoidable, as it is due to inappropriate prescribing.