Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation

Jin Wi, Hayeon Noh, Kyoung Lok Min, Seungwon Yang, Byung Hak Jin, Jongsung Hahn, Soo Kyung Bae, Jiseon Kim, Min Soo Park, Donghoon Choi, Min Jung Chang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a 50% probability of target attainment at 72 h using a trough concentration target of 10 g/ml for mild to moderate infections and a trough concentration target of 15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

Original languageEnglish
Article numbere01015-17
JournalAntimicrobial agents and chemotherapy
Volume61
Issue number9
DOIs
Publication statusPublished - 2017 Sep

Fingerprint

Teicoplanin
Extracorporeal Membrane Oxygenation
Renal Replacement Therapy
Pharmacokinetics
Population
Infection
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Wi, Jin ; Noh, Hayeon ; Min, Kyoung Lok ; Yang, Seungwon ; Jin, Byung Hak ; Hahn, Jongsung ; Bae, Soo Kyung ; Kim, Jiseon ; Park, Min Soo ; Choi, Donghoon ; Chang, Min Jung. / Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation. In: Antimicrobial agents and chemotherapy. 2017 ; Vol. 61, No. 9.
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title = "Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation",
abstract = "The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a 50{\%} probability of target attainment at 72 h using a trough concentration target of 10 g/ml for mild to moderate infections and a trough concentration target of 15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)",
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Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation. / Wi, Jin; Noh, Hayeon; Min, Kyoung Lok; Yang, Seungwon; Jin, Byung Hak; Hahn, Jongsung; Bae, Soo Kyung; Kim, Jiseon; Park, Min Soo; Choi, Donghoon; Chang, Min Jung.

In: Antimicrobial agents and chemotherapy, Vol. 61, No. 9, e01015-17, 09.2017.

Research output: Contribution to journalArticle

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T1 - Population pharmacokinetics and dose optimization of teicoplanin during venoarterial extracorporeal membrane oxygenation

AU - Wi, Jin

AU - Noh, Hayeon

AU - Min, Kyoung Lok

AU - Yang, Seungwon

AU - Jin, Byung Hak

AU - Hahn, Jongsung

AU - Bae, Soo Kyung

AU - Kim, Jiseon

AU - Park, Min Soo

AU - Choi, Donghoon

AU - Chang, Min Jung

PY - 2017/9

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N2 - The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a 50% probability of target attainment at 72 h using a trough concentration target of 10 g/ml for mild to moderate infections and a trough concentration target of 15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

AB - The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a 50% probability of target attainment at 72 h using a trough concentration target of 10 g/ml for mild to moderate infections and a trough concentration target of 15 g/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.)

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