Renal elimination of cefoxitin and effect of probenecid after single and repeated doses

Plasma and urine concentrations of cefoxitin were measured by HPLC after single and repeated administration in 16 patients undergoing cob-rectal surgery. In eight patients the effect of probenecid pretreatment was evaluated and related to probenecid plasma levels. Repeated dosing caused a slight accumulation of cefoxitin in two patients on cefoxitin alone, and in two patients on combined treatment with probenecid. In the former the elimination half-life of cefoxitin was also increased. Cefoxitin renal clearance fell at probenecid plasma levels between 15 to 35 mg/l, the maximum effect being reached above 50 mg/l. Higher plasma levels of cefoxitin were obtained after pretreatment with probenecid. Since the elimination half-life of cefoxitin was little affected, this was mainly due to a decreased volume of distribution, Vβ. Six of the 16 patients showed a slight increase in serum creatinine after nine i.v. doses of cefoxitin (2 g) or cefoxitin (2 g) plus probenecid (0·5 g). Whether this was caused by the drug or by surgery itself was unclear. The renal clearance of cefoxitin appeared to be independent of the drug plasma concentration, in similarity to cefamandole but in contrast to cephapinn or cephaloridine.