Clinical Pharmacokinetics

, Volume 54, Issue 12, pp 1273–1285 | Cite as

Pharmacokinetic Studies in Neonates: The Utility of an Opportunistic Sampling Design

  • Stéphanie Leroux
  • Mark A. Turner
  • Chantal Barin-Le Guellec
  • Helen Hill
  • Johannes N. van den Anker
  • Gregory L. Kearns
  • Evelyne Jacqz-Aigrain
  • Wei ZhaoEmail author
  • On behalf of the TINN (Treat Infections in NeoNates) and GRiP (Global Research in Paediatrics) Consortiums
Original Research Article


Background and Objective

The use of an opportunistic (also called scavenged) sampling strategy in a prospective pharmacokinetic study combined with population pharmacokinetic modelling has been proposed as an alternative strategy to conventional methods for accomplishing pharmacokinetic studies in neonates. However, the reliability of this approach in this particular paediatric population has not been evaluated. The objective of the present study was to evaluate the performance of an opportunistic sampling strategy for a population pharmacokinetic estimation, as well as dose prediction, and compare this strategy with a predetermined pharmacokinetic sampling approach.


Three population pharmacokinetic models were derived for ciprofloxacin from opportunistic blood samples (SC model), predetermined (i.e. scheduled) samples (TR model) and all samples (full model used to previously characterize ciprofloxacin pharmacokinetics), using NONMEM software. The predictive performance of developed models was evaluated in an independent group of patients.


Pharmacokinetic data from 60 newborns were obtained with a total of 430 samples available for analysis; 265 collected at predetermined times and 165 that were scavenged from those obtained as part of clinical care. All datasets were fit using a two-compartment model with first-order elimination. The SC model could identify the most significant covariates and provided reasonable estimates of population pharmacokinetic parameters (clearance and steady-state volume of distribution) compared with the TR and full models. Their predictive performances were further confirmed in an external validation by Bayesian estimation, and showed similar results. Monte Carlo simulation based on area under the concentration–time curve from zero to 24 h (AUC24)/minimum inhibitory concentration (MIC) using either the SC or the TR model gave similar dose prediction for ciprofloxacin.


Blood samples scavenged in the course of caring for neonates can be used to estimate ciprofloxacin pharmacokinetic parameters and therapeutic dose requirements.


Full Model Predictive Performance Population Pharmacokinetic Model Objective Function Value Pharmacokinetic Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the UK National Institute for Health Research for supporting the delivery of the ciprofloxacin trial, and the clinical teams at Liverpool Women’s National Health Service Foundation Trust (NHS FT) (Tim Neal, Christine Chesters) and Alder Hey Children’s NHS FT (Sarah Mahoney, Stephane Paulus), Liverpool, UK.


This work was supported by the TINN (Treat Infections in NeoNates, European Commission FP7 project, Grant Agreement Number 223614), the GRIP (Global Research in Paediatrics, European Commission FP7 project, Grant Agreement Number 261060), and The Fundamental Research Funds of Shandong University.

Conflicts of interest

Stéphanie Leroux, Mark A. Turner, Chantal Barin-Le Guellec, Helen Hill, Johannes N. van den Anker, Gregory L. Kearns, Evelyne Jacqz-Aigrain, and Wei Zhao declare no conflicts of interest relating to this work.

Ethical approval

All procedures in this study were in accordance with the 1964 Helsinki declaration (and its amendments). The study was approved by the institutional ethics board and independent ethics board of the TINN project (EudraCT 2010-019955-23), and was also monitored by an independent safety monitoring board.

Informed consent

Parental written consent to participate was obtained.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Stéphanie Leroux
    • 1
    • 2
    • 3
    • 4
  • Mark A. Turner
    • 5
    • 6
  • Chantal Barin-Le Guellec
    • 7
  • Helen Hill
    • 5
    • 6
  • Johannes N. van den Anker
    • 8
    • 9
    • 10
    • 11
  • Gregory L. Kearns
    • 12
    • 13
  • Evelyne Jacqz-Aigrain
    • 1
    • 2
    • 3
    • 14
  • Wei Zhao
    • 1
    • 2
    • 3
    • 14
    • 15
    Email author
  • On behalf of the TINN (Treat Infections in NeoNates) and GRiP (Global Research in Paediatrics) Consortiums
  1. 1.Sino-French Pediatric Research Center, Department of Clinical Pharmacy, School of Pharmaceutical SciencesShandong UniversityJinanChina
  2. 2.Department of Pediatric Pharmacology and PharmacogeneticsHôpital Robert Debré, APHPParisFrance
  3. 3.EA7323Université Paris Diderot, Sorbonne Paris CitéParisFrance
  4. 4.Department of NeonatologyCHU de RennesRennesFrance
  5. 5.Department of Women’s and Children’s Health, Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK
  6. 6.Neonatal UnitLiverpool Women’s HospitalLiverpoolUK
  7. 7.EA4245, Faculté de MédecineUniversité François RabelaisToursFrance
  8. 8.Intensive CareErasmus MC - Sophia Children’s HospitalRotterdamThe Netherlands
  9. 9.Division of Pediatric Clinical PharmacologyChildren’s National Medical CenterWashingtonUSA
  10. 10.Departments of Pediatrics, Pharmacology and PhysiologyGeorge Washington University, School of Medicine and Health SciencesWashingtonUSA
  11. 11.Department of Paediatric PharmacologyUniversity Children’s Hospital BaselBaselSwitzerland
  12. 12.Division of Clinical Pharmacology and Therapeutic Innovationthe Children’s Mercy HospitalKansas CityUSA
  13. 13.Department of PediatricsUniversity of Missouri–Kansas CityKansas CityUSA
  14. 14.Clinical Investigation Center CIC1426INSERMParisFrance
  15. 15.Department of PharmacyQianfoshan Hospital Affiliated to Shandong UniversityJianChina

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