Ken-ichi Oguchi

Pharmacokinetic Study of Antimicrobial Agents in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

A pharmacokinetic study was done in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) to establish an appropriate treatment for bacterial peritonitis. Twenty-nine CAPD patients were randomized to receive either oral ofloxacin (OFLX) 300 mg, followed by 200 mg once a day; intraperitoneal vancomycin (VCM) 30 mg/kg once a week; or intravenous imipenem/cilastatin (IPM/CS) 1000 mg once a day. Pharmacokinetic simulation models were determined according to changes of doses and duration. The time to reach the maximum plasma concentration (tmax), the maximum plasma concentration (Cmax), the plasma elimination half-life (t1/2), and area under the curve (AUC) were, respectively, 5.2 hours, 4.7 μg/mL, 20.4 hours and 80.5 μg/mL/h (AUC0–24) for OFLX, 7.0 h, 26.4 μg/mL, 92.0 hours, and 1641 μg/mL/h (AUC0–120) for VCM, 1.1 hour, 62.3 μg/ml, 3.76 hours, and 229.3 μg/mL/h (AUC0−1) for IPM/CS. Twenty-three of 27 (85%) strains of clinical isolates were gram-positive cocci; 20 strains (74%) consisted of staphylococci or streptococci. The MIC90 of OFLX, VCM, and IPM was 3.13, 1.56, and 0.78 μg/mL, respectively. When the minimum concentration in the dialysate during the initial 5 days was higher than the MIC, all the isolates (7 out of 7) were eradicated, when it was lower, only half of the isolates (3 out of 6) were eradicated. The simulation study suggested a significant drug accumulation in response to shortening the dosing duration.