Removal of Doripenem During Hemodialysis and the Optimum Dosing Regimen for Patients Undergoing Hemodialysis

Abstract

The removal of doripenem by hemodialysis was studied in six hemodialysis patients. Following an intravenous drip infusion of 0.5 g of doripenem, plasma concentrations of the drug were measured. The decrease in drug concentrations in plasma was observed during various periods of non-hemodialysis, and hemodialysis accelerated the elimination of doripenem. For example, the calculated mean half-life during hemodialysis was significantly shorter than that during non-hemodialysis periods (P = 0.002). The calculated pharmacokinetic parameters indicated that the mean rate of decrease in plasma concentration due to hemodialysis alone was 56.12 ± 8.11%. Upon obtaining these results and several pharmacokinetic parameters, we attempted to optimize the dosing regimen of doripenem for hemodialysis patients. We recommend the use of 0.25 g of doripenem once a day in patients infected with viable bacteria, and in patients who are infected with Pseudomonas aeruginosa, 0.5 g twice a day on the first day of administration, followed by 0.5 g once a day.

Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy

“…Clearance differences between hemodialysis and hemodiafiltration were negligible. Compared to an earlier report describing doripenem pharmacokinetics during hemodialysis, our patients were treated with higher blood flow rates (7). As a consequence of the higher dose administered, maximum doripenem plasma concentrations exceeded those presented earlier (67.0 Ϯ 24.8 mg/liter versus 24.56 Ϯ 11.20 mg/liter) (7).…”

“…As a consequence of the higher dose administered, maximum doripenem plasma concentrations exceeded those presented earlier (67.0 Ϯ 24.8 mg/liter versus 24.56 Ϯ 11.20 mg/liter) (7). The prefilter/postfilter clearance values found in our trial are in line with those described by Tanoue et al (123.5 Ϯ 42.0 ml/min versus 117.78 Ϯ 20.50 ml/min) (7). Compared to historic data for doripenem (83.83 Ϯ 7.11 ml/min) or meropenem (79 to 81 ml/min), doripenem was cleared to a larger extent in our trial (15,18).…”

“…Compared to an earlier report describing doripenem pharmacokinetics during hemodialysis, our patients were treated with higher blood flow rates (7). As a consequence of the higher dose administered, maximum doripenem plasma concentrations exceeded those presented earlier (67.0 Ϯ 24.8 mg/liter versus 24.56 Ϯ 11.20 mg/liter) (7). The prefilter/postfilter clearance values found in our trial are in line with those described by Tanoue et al (123.5 Ϯ 42.0 ml/min versus 117.78 Ϯ 20.50 ml/min) (7).…”

“…In adult patients in need of intermittent renal replacement therapy (iRRT), the suggested dosage for doripenem ranges from 0.25 to 0.5 g once daily (6,7). However, most patients undergoing iRRT are treated in an outpatient setting; therefore, a posthemodialysis antimicrobial regimen would be desirable for such patients, as well as preferable from an economic viewpoint (8).…”

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

“…Doripenem was not absorbed onto AN69ST, polymethylmethacrylate, and polysulfone membranes (Hiraiwa et al, 2020). CVVHD could accelerate the elimination of doripenem (Tanoue et al, 2011). The initial dosing recommendation of doripenem for renally competent patients was 500 mg q8h.…”