Pharmacokinetics and Administration Regimens of Vancomycin in Neonates, Infants and Children

Abstract

The increased use of vancomycin in neonatal and paediatric patients has prompted numerous pharmacokinetic studies and the development of many empirical administration methods. The majority of dosage guidelines use the relationship between pharmacokinetic parameters and patient variables such as chronological age, bodyweight, and/or measures of renal function. Currently, those dosage guidelines which are based upon postconceptional age and bodyweight seem to provide the best options for empirical administration in neonates and infants. In addition, serum creatinine may prove to be a useful guide to the empirical administration of vancomycin in neonates older than 7 to 14 days. Several investigators have reported the individualisation of dosage regimens based on pharmacokinetic-based administration methods. The most common techniques employed have been Sawchuk-Zaske method and Bayesian forecasting. However, only a limited number of studies have evaluated either empirical administration or individualised administration techniques in patient populations outside those of the original reports; this makes choosing between the methods difficult. Pharmacokinetic data and administration recommendations have gradually become available in special paediatric patient populations. The majority of studies have focused on patients requiring cardiopulmonary bypass surgery or with burns, cancer or central nervous system infections. However, a limited amount of information is available regarding vancomycin disposition in children older than 1 year of age with and without end-stage renal failure. The monitoring of serum vancomycin concentrations may be useful in selected neonatal and paediatric patient populations, especially where large interpatient variability occurs and administration guidelines are not clearly established. Similar to the literature on adults, the lack of conclusive evidence concerning the relationship between serum vancomycin concentrations and therapeutic responses leaves this topic open to debate.

A Population Pharmacokinetic Model for Vancomycin in Pediatric Patients and Its Predictive Value in a Naive Population

“…Likewise, others have found that the PK of VAN is better described by a two-instead of a one-compartment PK model (6,9,11). Body weights and creatinine clearances used as covariates in the model allowed significant reduction of the interindividual and residual variability.…”

Population Pharmacokinetics of Vancomycin in Premature Malaysian Neonates: Identification of Predictors for Dosing Determination

“…Dosing practices have relied solely on literature data from Caucasian infants. Besides elucidating any alteration in pharmacokinetic parameter values, it was important to obtain estimates of the variability in this population since high interindividual pharmacokinetic variability is a feature of antimicrobial pharmacotherapeutics in premature infants (33). Accordingly, the aim of present study was to conduct a population pharmacokinetic analysis in order to obtain pharmacokinetic data for vancomycin in premature Malaysian infants.…”

Vancomycin Pharmacokinetics in Preterm Infants

“…14,[18][19][20][21] The trough plasma concentration of vancomycin seems to be the most important parameter for drug monitoring since it is directly related to the therapeutic efficacy of the antibiotic agent. The adequate value is based on the blood level that must exceed by 2 to 8 times the minimal inhibitory concentration for Staphylococcus species.…”