Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation [PublishAheadOfPrint]

Pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical PK studies of drugs administered during ECMO are scarce and proper dosing adjustment is 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. PK samples were collected from ten adult patients, and a population PK analysis as well as simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 hours using a trough concentration target of >10 μg/mL for mild to moderate infections and of >15 μg/mL for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. Presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) 600 mg and a maintenance dose (MD) 400 mg for ECMO patients not receiving CRRT; and a LD 800 mg and a MD 600 mg for those receiving CRRT. For severe infections, an optimal dose was a LD 1000 mg and a MD 800 mg for ECMO patients not receiving CRRT; and a LD 1200 mg and a MD 1000 mg for those receiving CRRT. In conclusion, higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO.

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