FACTORS INFLUENCING THE ABSORPTION AND DISPOSITION OF MECILLINAM AND PIVMECILLINAM IN MAN

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Abstract
1 In a pharmacokinetic study in six volunteers peak serum mecillinam concentrations were proportional to the oral dose of pivmecillinam at two dose levels of 200 and 400 mg. 2 Effects of bed rest, probenecid and a 6 day course of treatment with pivmecillinam on serum mecillinam concentrations after an oral dose of pivmecillinam (two 200 mg capsules) have been investigated. 3 Resting subjects had lower peak serum levels and a decreased rate of clearance than moderately active subjects, changes which are similar to those previously reported for benzylpenicillin. 4 Pretreatment with probenecid produced significantly higher serum mecillinam levels, a longer serum antibiotic half-life and a decreased rate of drug clearance which suggests that mecillinam is actively excreted by kidney tubules. 5 Plasma mecillinam level profiles obtained after the first dose of a 6 day treatment period were not significantly different from corresponding values after the first dose on the seventh day which indicates that each dose of mecillinam is eliminated in healthy young adults before succeeding doses are taken.