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 language | English |
|---|---|
| Article number | e01015-17 |
| Journal | Antimicrobial agents and chemotherapy |
| Volume | 61 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2017 Sep |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
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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 journal › Article
TY - JOUR
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
Y1 - 2017/9
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.)
UR - http://www.scopus.com/inward/record.url?scp=85028339487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028339487&partnerID=8YFLogxK
U2 - 10.1128/AAC.01015-17
DO - 10.1128/AAC.01015-17
M3 - Article
C2 - 28674057
AN - SCOPUS:85028339487
VL - 61
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 9
M1 - e01015-17
ER -