Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing

Jitmuang, Anupop; Nation, Roger L.; Koomanachai, Pornpan; Chen, Gong; Lee, Hee Ji; Wasuwattakul, Somkiat; Sritippayawan, Suchai; Li, Jian; Thamlikitkul, Visanu; Landersdorfer, Cornelia B.

doi:10.1093/jac/dkv031

Cited by 22 publications

(23 citation statements)

References 22 publications

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“…The CMS volume of distribution was moderately increased in ICU-HD patients compared with that in ICU-85 patients (Table 2), but, surprisingly, total clearance in ICU-HD patients (typical value, 113 ml/min) was virtually the same as that in ICU-85 patients (typical value, 112 ml/min). This result suggests that CMS nonrenal clearance (CL NRCMS ) is increased by approximately 2-fold (from 43.7 ml/min to 113 ml/ min) in HD patients, which was not seen in previous studies (5,8). Accordingly, CMS concentrations versus time profiles in typical ICU-HD and ICU-85 patients are virtually superimposed (Fig.…”

Section: This Study Allowed Comparisons Between Cms and Colistin Pk Imentioning

confidence: 58%

“…Second, the effect of HD sessions on colistin plasma concentrations was assessed by simulating 4-h HD sessions with different values of CMS and colistin HD clearances reported in the literature, i.e., 94.8, 90, and 94.8 ml/min for CMS and 56.7, 137, and 66.5 ml/min for colistin, respectively (5,7,8). For this simulation, PK parameter values-except HD clearances-were fixed to estimates of the present analysis, and the dosage regimen consisted of repeated administrations of CMS at 1.5 MIU every 12 h (q12h) and a supplemental reloading dose of 1.5 MIU administered along with the scheduled 1.5-MIU dose just after the HD session.…”

Section: Methodsmentioning

confidence: 99%

“…The CMS dose planned before the HD session was postponed to immediately after the session and was 3 MIU. Curves were simulated with different values of CMS and colistin HD clearances reported in the literature, i.e., 94.8, 90, and 94.8 ml/min for CMS and 56.7, 137, and 66.5 ml/min for colistin (solid grey line, solid black line, and dashed black line), respectively (5,7,8). PK parameter values-except HD clearances-were fixed to estimates of the present analysis.…”

Section: Fig 4 Simulations Of Colistin Plasma Concentration-time Profmentioning

confidence: 99%

“…Studies have also been conducted in critical care patients with acute renal failure requiring intermittent hemodialysis (HD) (5,(7)(8)(9). However, focus was placed on CMS and colistin clearance during HD rather than between two consecutive HD sessions.…”

mentioning

confidence: 99%

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Population Pharmacokinetics of Colistin Methanesulfonate and Colistin in Critically Ill Patients with Acute Renal Failure Requiring Intermittent Hemodialysis

Jacobs

Grégoire

Mégarbane

et al. 2016

Antimicrob Agents Chemother

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Colistin is increasingly used as a last option for the treatment of severe infections due to Gram-negative bacteria in critically ill patients requiring intermittent hemodialysis (HD) for acute renal failure. Our objective was to characterize the pharmacokinetics (PK) of colistin and its prodrug colistin methanesulfonate (CMS) in this population and to suggest dosing regimen recommendations. Eight intensive care unit (ICU) patients who were under intermittent HD and who were treated by CMS (Colimycine) were included. Blood samples were collected between two consecutive HD sessions. CMS and colistin concentrations were measured by a specific chromatographic assay and were analyzed using a PK population approach (Monolix software). Monte Carlo simulations were conducted to predict the probability of target attainment (PTA). CMS nonrenal clearance was increased in ICU-HD patients. Compared with that of ICU patients included in the same clinical trial but with preserved renal function, colistin exposure was increased by 3-fold in ICU-HD patients. This is probably because a greater fraction of the CMS converted into colistin. To maintain colistin plasma concentrations high enough (>3 mg/liter) for high PTA values (area under the concentration-time curve for the free, unbound fraction of a drug [fAUC]/MIC of >10 and fAUC/MIC of >50 for systemic and lung infections, respectively), at least for MICs lower than 1.5 mg/liter (nonpulmonary infection) or 0.5 mg/liter (pulmonary infection), the dosing regimen of CMS should be 1.5 million international units (MIU) twice daily on non-HD days. HD should be conducted at the end of a dosing interval, and a supplemental dose of 1.5 MIU should be administered after the HD session (i.e., total of 4.5 MIU for HD days). This study has confirmed and complemented previously published data and suggests an a priori clear and easy to follow dosing strategy for CMS in ICU-HD patients. Over the last several years, colistin (polymyxin E) has been increasingly used as a last option for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae (1, 2), for which the mortality rate has increased (3).Colistin is administered as a prodrug, colistin methanesulfonate (CMS), which is mostly excreted unchanged in urine (70%) and is partly converted to colistin (30% at most), whereas renal excretion of colistin is negligible (4). As a result, in patients with renal failure, a greater fraction of the CMS dose may be converted into colistin (5); therefore, all other things being equal, colistin plasma concentrations at steady state should increase. The elimination of colistin is nonrenal-it undergoes extensive renal tubular reabsorption-and nonbiliary by unknown mechanism (1).It has recently been shown that in intensive care unit (ICU) patients, colistin plasma concentrations at steady state are mostly governed by renal function and that creatinine clearance can be used for dosing regimen adaptation ...

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Section: This Study Allowed Comparisons Between Cms and Colistin Pk Imentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Fig 4 Simulations Of Colistin Plasma Concentration-time Profmentioning

confidence: 99%

mentioning

confidence: 99%

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Population Pharmacokinetics of Colistin Methanesulfonate and Colistin in Critically Ill Patients with Acute Renal Failure Requiring Intermittent Hemodialysis

Jacobs

Grégoire

Mégarbane

et al. 2016

Antimicrob Agents Chemother

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show abstract

“…For patients receiving intermittent RRT, it's suggested to give an additional dose of colistin methanesulfonate sodium after dialysis (77,88), but no standardized dose recommendations are currently available for these long-lasting modalities of intermittent RRT. For end-stage renal disease (ESRD) patients receiving intermittent hemodialysis (HD), evidence from 10 patients indicated that HD should be conducted at the end of a dosing interval and a supplemental dose should be administered (89). A report of 8 continuous ambulatory peritoneal dialysis (CAPD) patients suggested that CMS doses should not be increased during CAPD because clearance by CAPD was low for both CMS and formed colistin (90).…”

Section: Dosing Strategiesmentioning

confidence: 99%

Intravenous polymyxins: Revival with puzzle

Fei

et al. 2017

BST

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Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use

Nation

Forrest

2019

Advances in Experimental Medicine and Biology

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Extracorporeal clearance of colistin methanesulphonate and formed colistin in end-stage renal disease patients receiving intermittent haemodialysis: implications for dosing

Abstract: Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.

Cited by 22 publications

References 22 publications

Population Pharmacokinetics of Colistin Methanesulfonate and Colistin in Critically Ill Patients with Acute Renal Failure Requiring Intermittent Hemodialysis

Population Pharmacokinetics of Colistin Methanesulfonate and Colistin in Critically Ill Patients with Acute Renal Failure Requiring Intermittent Hemodialysis

Intravenous polymyxins: Revival with puzzle

Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use

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