A study of the pharmacokinetics and tolerability of ritipenem acoxil in healthy volunteers following multiple oral dosing.

The pharmacokinetics of ritipenem acoxil, the oral prodrug of the antibiotic ritipenem, were studied in volunteers after single and repeated dosing (500 mg, three times daily for 10 days). Concentrations of ritipenem and open beta-lactam ring metabolites were measured using HPLC/UV. Ritipenem did not accumulate significantly in plasma, owing to its half-life of about 0.7 h; the area under the curve for 0-8 h was on average about 10 mg x h/L. Plasma pharmacokinetics of ritipenem and metabolites were time-independent. A decrease of ritipenem renal clearance (87 versus 132 mL/min) and a slight increase in the amount of metabolites excreted in urine were observed following repeated dosing.