Format

Send to

Choose Destination
Antimicrob Agents Chemother. 2017 Aug 24;61(9). pii: e01015-17. doi: 10.1128/AAC.01015-17. Print 2017 Sep.

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation.

Author information

1
Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
2
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea.
3
Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea.
4
Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
5
College of Pharmacy, The Catholic University of Korea, Bucheon, Republic of Korea.
6
Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
7
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea mjchang@yonsei.ac.kr.

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 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/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.).

KEYWORDS:

cardiogenic shock; extracorporeal membrane oxygenation; pharmacokinetics; population pharmacokinetics; teicoplanin

PMID:
28674057
PMCID:
PMC5571348
DOI:
10.1128/AAC.01015-17
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center