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External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates

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Abstract

Background and Objective

Vancomycin is the drug of choice in the treatment of MRSA infections. In a published vancomycin population pharmacokinetic study on neonates in Singapore healthcare institutions, it was found that vancomycin clearance was predicted by weight, postmenstrual age, and serum creatinine. The aim of this study was to externally validate the vancomycin population pharmacokinetic model to develop a new dosage regimen in neonates, and to compare this regimen with the existing institutional and NeoFax® dosage regimens.

Methods

A retrospective chart review of neonates who received vancomycin therapy and therapeutic drug monitoring was conducted. The median prediction error percentage was calculated to assess bias, while the median absolute prediction error percentage and the root mean squared error percentage were calculated to assess precision. The new dosage regimen was developed using Monte Carlo simulation.

Results

A total of 20 neonates were included in the external validation dataset. Eighteen of them were premature, with a median gestational age of 27.7 (25.9–31.5) weeks and postmenstrual age of 30.5 (27.3–34.3) weeks at the point of vancomycin initiation. No apparent systematic bias was found in the predictions of the model. The external validation performed in the current study found the model to be generally unbiased. Our new vancomycin dosage regimen was able to achieve target trough concentrations and area under the curve (AUC24) at a greater proportion as compared to existing institutional and NeoFax® dosage regimens.

Conclusion

The pharmacokinetic model built in the previous study can be used to conduct reliable population simulations of our Asian neonatal population in Singapore. The new dosage regimen was able to achieve target trough concentrations and AUC24 better than existing institutional and NeoFax® dosage regimens.

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Acknowledgements

We thank Dr Sing Teang Kong for her valuable input on the external validation of our vancomycin pharmacokinetic model.

Author information

Author notes

  1. Chuan Poh Lim and Sheng Hsuan Tseng have joint first authorship.

Authors and Affiliations

  1. Department of Pharmacy, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore

    Chuan Poh Lim

  2. Department of Pharmacy, National University Hospital, Kent Ridge Road, Singapore, 119074, Singapore

    Sheng Hsuan Tseng & Cheryl Chia Chin Neoh

  3. Department of Pharmacy, KK Women’s and Children’s Hospital, Bukit Timah Road, Singapore, 229899, Singapore

    Qi Chen

  4. Department of Neonatal and Developmental Medicine, Singapore General Hospital, Outram Road, Singapore, 169608, Singapore

    Woei Bing Poon

Authors
  1. Chuan Poh Lim
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  2. Sheng Hsuan Tseng
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Corresponding author

Correspondence to Chuan Poh Lim.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Ethics Approval

This retrospective chart review study was in line with the principles of the Declaration of Helsinki. Approval was granted by the NHG Domain Specific Review Board.

Consent to Participate

A waiver of informed consent was granted by the NHG Domain Specific Review Board.

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Not applicable.

Author Contributions

All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Chuan Poh Lim and Sheng Hsuan Tseng. The first draft of the manuscript was written by Chuan Poh Lim and Sheng Hsuan Tseng. All authors commented on previous versions of the manuscript and read and approved the final manuscript.

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Lim, C.P., Tseng, S.H., Neoh, C.C.C. et al. External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates. Eur J Drug Metab Pharmacokinet 47, 687–697 (2022). https://doi.org/10.1007/s13318-022-00781-w

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  • DOI: https://doi.org/10.1007/s13318-022-00781-w

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