Pharmacokinetics and tolerance of cefuroxime axetil in volunteers during repeated dosing

A total of 158 volunteers each received 21 repeated oral doses of 500 mg of cefuroxime axetil (CAE) during four comparative cross-over trials. Pharmacokinetics were studied in 8 volunteers (CAE versus ampicillin), relative bioavailability and tolerance were studied in 100 volunteers (CAE versus pivmecillinam and CAE versus pivampicillin), and tolerance alone was studied in 50 volunteers (CAE versus ampicillin). Overall, urinary recoveries of the active antibiotics ranked absorption of the drugs in the order least to greatest: pivmecillinam, ampicillin, CAE, and pivampicillin. The pharmacokinetics of CAE and ampicillin did not change after repeated dosing. Peak serum levels of cefuroxime were significantly higher than those of ampicillin after doses 1 and 21 but the urinary recoveries of both antibiotics were around 35% of the dose. CAE was as well tolerated as ampicillin but there were smaller numbers of episodes of fluid bowel motions on pivmecillinam and pivampicillin than on CAE, which may have been due to the smaller amounts of active antibiotic in the doses of the pivaloyloxymethyl esters.