title: Effect of orally administered probenecid on the pharmacokinetics of cefoxitin.
abstract: To characterize the effect of orally administered probenecid on the pharmacokinetics of cefoxitin in healthy male volunteers, we administered to one group of six subjects 2 g of cefoxitin by intravenous (i.v.) bolus either alone, with 1 g of probenecid concomitantly, or when 1 g of probenecid was administered 1 h previously by using a crossover design. Likewise, we administered to a second group of six subjects 2 g of cefoxitin intramuscularly (i.m.) together with 1 and 2 g of probenecid. Probenecid increased the mean terminal half-life and the area under the serum cefoxitin concentration-time curve (AUC0-24) and decreased renal clearance, but did not alter the volume of the central compartment or the total urinary recovery of i.v.-administered cefoxitin; pretreatment with probenecid produced a greater increase in cefoxitin AUC0-24 and a constant decrease in renal clearance compared to concomitant probenecid. The AUC0-24 after i.m.-administered cefoxitin was greater after 2 g than 1 g of probenecid; the AUC0-24 after i.v.-and i.m.-administered cefoxitin was similar after 1 g of probenecid was given concomitantly. Cefoxitin AUC0-24 was increased further when 1 g of probenecid was given before i.v.-administered cefoxitin or when 2 g of probenecid was given with i.m.-administered cefoxitin. The effect of probenecid was related to both timing and dose.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002440:Cefoxitin / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011339:Probenecid / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002440:Cefoxitin; D011339:Probenecid