Doripenem Pharmacokinetics in Critically Ill Patients Receiving Continuous Hemodiafiltration (CHDF)

Hidaka, Seigo; Goto, Koji; Hagiwara, Satoshi; Iwasaka, Hideo; Noguchi, Takayuki

doi:10.1248/yakushi.130.87

Cited by 26 publications

(27 citation statements)

References 17 publications

(8 reference statements)

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“…7) Two patients (ID 7, 8) received a single dose of doripenem (250 mg). Doripenem (250 mg; Shionogi & Co., Ltd., Japan) was dissolved in 20 ml of normal saline solution and administered as an intravenous drip over 1 h/session.…”

Section: Methods Doripenem Administration and Collection Of Blood Sammentioning

confidence: 99%

“…Six patients (ID 1 6) participated in our previous study. 7) All patients had severe renal dysfunction, with creatinine clearances (C cr , an indicator of residual renal function) that ranged from 3.7 to 15.0 ml/min (mean, 9.54 ml/min). Residual diuresis was not extensive in any patient during the study period.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Data for conventional CHDF were reported in a previous study. 7) 1397 No. 9 Pharmacokinetics Time Course of Plasma DRPM Concentration Figure 1 shows a time course of plasma doripenem concentrations after theˆrst dose in the standard-and high-‰ow groups.…”

Section: Fig 1 Plasma Concentration-time Proˆles Of Doripenemmentioning

confidence: 99%

“…Studies on the pharmacokinetics of one particular antibiotic, the carbapenem antibiotic doripenem (DRPM), while performing conventional CHDF 7,8) have shown that DRPM clearance during CHDF was 13.5 ml/min using CHDF parameters typically used in Japan (blood ‰ow rate (Q B ) 100 ml/ min, dialysate ‰ow rate (Q D ) 500 ml/h,ˆltration ‰ow rate (Q F ) 300 ml/h). These results showed that the pharmacokinetics of DRPM depended primarily on residual renal function and that CHDF had little impact.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we investigated the pharmacokinetics of DRPM in patients receiving high‰ow CHDF and compared it to that in patients receiving conventional-dose CHDF. 7) SUBJECTS AND METHODS…”

Section: Introductionmentioning

confidence: 99%

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Effect of Hemopurification Rate on Doripenem Pharmacokinetics in Critically Ill Patients Receiving High-flow Continuous Hemodiafiltration

et al. 2011

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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-volumeˆltration/ 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 (Q B ) of 100 ml/min, dialysate ‰ow rate (Q D ) of 500 ml/h, and ltration ‰ow rate (Q F ) of 300 ml/h. For the high-‰ow group, CHDF was performed at a blood ‰ow rate (Q B ) of 100 ml/min, dialysate ‰ow rate (Q D ) of 1500 ml/h, andˆltration ‰ow rate (Q F ) of 900 ml/h. For both groups, a polysulfonehemoˆlter with a membrane area of 1.0 m 2 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.

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Section: Methods Doripenem Administration and Collection Of Blood Sammentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Fig 1 Plasma Concentration-time Proˆles Of Doripenemmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Hemopurification Rate on Doripenem Pharmacokinetics in Critically Ill Patients Receiving High-flow Continuous Hemodiafiltration

et al. 2011

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Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock

Tamme

Oselin

Kipper

et al. 2014

The Journal of Clinical Pharma

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Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.

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Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

Lewis

Kays

Mueller

2016

The Journal of Clinical Pharma

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Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14-16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre- and post-PIRRT. Ertapenem 500 mg followed by 500 mg post-PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation.

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Doripenem Pharmacokinetics in Critically Ill Patients Receiving Continuous Hemodiafiltration (CHDF)

Cited by 26 publications

References 17 publications

Effect of Hemopurification Rate on Doripenem Pharmacokinetics in Critically Ill Patients Receiving High-flow Continuous Hemodiafiltration

Effect of Hemopurification Rate on Doripenem Pharmacokinetics in Critically Ill Patients Receiving High-flow Continuous Hemodiafiltration

Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock

Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

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