Plasma concentrations and excretion of mecillinam after oral administration of pivmecillinam in elderly patients

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Abstract
The pharmacokinetics of mecillinam have been studied in 6 elderly patients. A mean peak mecillinam concentration of 2.3 mg/l was obtained at 2.5 h in the serum of elderly (over 65 years) patients after a 400 mg oral dose of pivmecillinam. The corresponding mean peak serum concentration in young (less than 30 years) subjects is 2.6 mg/l. There was no significant difference between the rates of absorption for the two groups, the mean absorption rate constants (Ka) being 0.55 h−1 and 0.83 h−1 for the young and old respectively. The serum elimination half-life was markedly prolonged (3.97 h) in the elderly patients, despite apparently normal renal function, as compared with that in young volunteers (0.88 h). The difference in the corresponding elimination rate constants (K*1), 0.38 h−1 and 0.80 h−1 was significant (P=< 0.01). The observed difference in elimination half-life therefore appears to be due to a decreased ability in the elderly to eliminate mecillinam. This finding is reflected in the urinary mecillinam concentrations which in three of the elderly patients were less than 100 mg/1. These findings suggest that an increased dose of mecillinam may be necessary for the treatment of urinary tract infection in the elderly.

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