Pharmacokinetics and tolerance of a 24-h infusion of cefotetan disodium (with and without loading dose) in normal Caucasian volunteers

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Abstract
Cefotetan disodium has been given by zero order intravenous infusion at 75.8 mg/h to four healthy male volunteers over a 24-h period. Plasma concentrations rose until by 12 hs a mean steady state value of 37-5 mg/l was attained. In an additional four volunteers a loading dose of 0.5 g cefotetan was given immediately prior to a similar infusion. In these subjects concentrations in excess of the final steady-state value of 36.2 mg/l were achieved immediately and concentrations never fell below this value for the entire 24-h period of the study. The dose was well tolerated with the exception of an incidence of diarrhoea (2/8 mild and 1/8 severe). The pharmacokinctic findings are in good agreement with theoretical predictions based on single intravenous bolus doses of cefotetan and suggest that a loading dose, followed by an infusion would be suitable regime for cases of severe infection.

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