Influence of probenecid on serum levels and urinary excretion of cinoxacin.
Serum levels and urinary excretion of cinoxacin were examined in healthy individuals after a two-step intravenous infusion in the presence and absence of probenecid. After dosing cinoxacin alone, steady-state serum levels were approached in 1 h and were maintained for an additional 2 h with a reduced infusion rate. After probenecid pretreatment, serum levels of cinoxacin continued to increase during 3 h of infusion, reaching levels approximately double those obtained with cinoxacin alone. The mean elimination half-life of cinoxacin from serum was increased from 1.3 to 3.5 h in the presence of probenecid, and renal clearance was significantly reduced, with 46% of dosed drug appearing in 7-h urines of probenecid-treated subjects compared with 68% in subjects receiving cinoxacin alone. Probenecid had no apparent influence on cinoxacin distribution in the body but caused a significant decrease in the rate of cinoxacin extrarenal elimination, possibly due to competition for a common metabolic pathway.
D000328:Adult; D000892:Anti-Infective Agents, Urinary / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004148:Dioxolanes / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004149:Dioxoles / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008297:Male; D011339:Probenecid / Q000494:pharmacology*; D011724:Pyridazines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
D000892:Anti-Infective Agents, Urinary; D004148:Dioxolanes; D004149:Dioxoles; D011724:Pyridazines; D011339:Probenecid