EŠect of Hemopuriˆcation Rate on Doripenem Pharmacokinetics in Critically Ill Patients Receiving High-‰ow Continuous Hemodiaˆltration

Hemopuriˆcation is an eŠective therapy for acute kidney injury, deˆned as creatinine clearance less than 30 ml/ min, which occurs frequently in the intensive care unit. These critically ill patients often have severe infectious complications and are thus often treated with antibiotics. However, the eŠect of hemopuriˆcation on the pharmacokinetics of antibiotics is not well understood. In this study, we investigated the pharmacokinetics of doripenem (DRPM) in critically ill patients with accompanying renal dysfunction undergoing continuous hemodiaˆltration by high-volume ˆltration/ high-‰ow dialysis (high-‰ow CHDF) and compared it to the pharmacokinetics of DRPM during conventional CHDF. We studied 8 patients (2 in the high-‰ow group and 6 in the conventional group) in whom DRPM was administered while performing CHDF for acute kidney injury. DRPM (250 mg) was intravenously infused over 1 h. For the conventional group, CHDF was performed at a blood ‰ow rate (QB) of 100 ml/min, dialysate ‰ow rate (QD) of 500 ml/h, and ˆltration ‰ow rate (QF) of 300 ml/h. For the high-‰ow group, CHDF was performed at a blood ‰ow rate (QB) of 100 ml/min, dialysate ‰ow rate (QD) of 1500 ml/h, and ˆltration ‰ow rate (QF) of 900 ml/h. For both groups, a polysulfonehemoˆlter with a membrane area of 1.0 m2 was used. Mean half-life, total body clearance, and clearance via hemodiaˆltration of DRPM were 2.9 h, 118 ml/min, and 41.9 ml/min, respectively, in the high-‰ow group, and 7.9 h, 58 ml/min, and 13.5 ml/min in the conventional group. Clearance via hemodiaˆltration increased approximately 3-fold by tripling the hemopuriˆcation rate. Therefore, CHDF parameters greatly aŠected DRPM pharmacokinetics in patients receiving CHDF. These results suggest that clearance via hemodiaˆltration increases proportionally to the hemopuriˆcation rate. Thus, it is reasonable to conclude that DRPM dose must be increased to 1.01.5 g/day when performing high-‰ow CHDF.