title: Multiple-dose pharmacokinetics of amdinocillin in healthy volunteers.
abstract: The pharmacokinetics of amdinocillin (mecillinam) after multiple intravenous doses to healthy subjects are described. Assay of plasma and urine samples was carried out with a sensitive and specific high-pressure liquid chromatographic technique. A dose of 10 mg/kg of body weight was administered every 4 h for six doses. No accumulation was noted. Mean peak plasma concentrations were approximately 50 micrograms/ml, and the plasma half-life was approximately 53 min. Total plasma clearance was 4.6 ml/min per kg after the first dose, which declined slightly to 4.1 ml/min per kg after the last dose. Renal clearance remained fairly constant at approximately 2.9 ml/min per kg, or twice the creatinine clearance. The fraction excreted unchanged totaled 63% during the 4-h interval after the first dose and was nearly 70% overall. The steady-state volume of distribution was calculated to be 0.26 liter/kg. Urinary concentrations of amdinocillin were far in excess of the usual inhibitory concentrations for susceptible pathogens and were as high as 3,000 micrograms/ml. Dose of amdinocillin every 4 h provide plasma and urine concentrations which should be effective for the treatment of infections.
mesh_terms: D000328:Adult; D000560:Amdinocillin / Q000008:administration & dosage / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010397:Penicillanic Acid; D000560:Amdinocillin