Effect of age on single- and multiple-dose pharmacokinetics of erythromycin

The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d. for 7 doses. The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses. Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively). The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h). No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution. The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults. Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance. The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people.