Instructions for use Title Pharmacokinetics and the most suitable regimen of panipenem / beta mipron in critically ill patients receiving continuous renal replacement therapy : a pilot study

1 Title Pharmacokinetics and the most suitable regimen of panipenem/betamipron in critically ill patients receiving continuous renal replacement therapy-a pilot study Suitable regimen of PAPM/BP during CRRT Key words pharmacokinetics carbapenems kidney failure hemofiltration metabolic clearance rate 2 Abstract Critically ill patients are often complicated with acute renal failure induced by severe infection or sepsis. The patients need administration of broad-spectrum antibiotics as well continuous renal replacement therapy (CRRT). However, there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT is performed with the various combinations of dialysate flows (Q D) and ultrafiltrate flows (Q F). The aims of this study were to estimate the pharmacokinetics of panipenem/betamipron (PAPM/BP) and to determine the appropriate treatment regimens for PAPM/BP in critically ill patients undergoing CRRT. In patients with CRRT, the PAPM total clearance (PAPM CL tot) was calculated as the sum of PAPM clearance dependent on the living body and CRRT and shown as follow: PAPM CL tot (ml/min) = (1.2 CL cre + 66.5) + 0.86 (Q D +Q F) where CL cre is creatinine clearance. Pharmacokinetic values of PAPM were measured in 4 patients with CRRT. According to these results, the most appropriate treatment regimen regarding PAPM CL tot (ml/min) showed as follows: PAPM CL tot < 80 0.5 g every 12 hr or 1 g every 15 hr PAPM CL tot 80-120 0.5 g every 8 hr or 1 g every 12 hr PAPM CL tot 120-160 0.5 g every 6 hr or 1 g every 8 hr 3 Critically ill patients are often complicated with acute renal failure and thus are hemodynamically unstable. Continuous renal replacement therapy (CRRT) has proven to be a convenient extracorporeal technique to treat renal failure and subsequent fluid overload in critically ill patients. However, there is no uniformity in the pharmacokinetics of drugs used during CRRT because the procedure is performed with the use of many different combinations of dialysate flows (Q D) and ultrafiltrate flows (Q F). Critically ill patients are also often complicated with various severe infections and need to be intravenously administrated antibiotics with a broad spectrum. For critically ill patients with various severe infections, panipenem/betamipron (PAPM/BP) is often intravenously administered because it demonstrates good clinical and bacteriological efficacy 1. Panipenem is carbapenem that has a broad spectrum of activity covering gram-negative and gram-positive aerobic and anaerobic bacteria 1,2. Panipenem is administered with BP, an organic anion …