Medical Microbiology and Immunology

, Volume 207, Issue 5–6, pp 339–343 | Cite as

Lopinavir serum concentrations of critically ill infants: a pharmacokinetic investigation in South Africa

  • Michael SchultheißEmail author
  • Sharon Kling
  • Ulrike Lenker
  • Miriam von Bibra
  • Bernd Rosenkranz
  • Hartwig Klinker
Rapid Communication


The role of therapeutic drug monitoring in pediatric antiretroviral therapy is unclear. A little pharmacokinetic datum from clinical practice exists beyond controlled approval studies including clinically stable children. The aim of this study is to quantify LPV exposure of critically ill infants in an ICU and—by identifying risk factors for inadequate exposure—to define sensible indications for TDM in pediatric HIV care; in addition, assume total drug adherence in ICU to compare LPV exposure with a setting of unknown adherence. In this prospective investigation, 15 blood samples from critically ill infants in the pediatric ICU at Tygerberg Hospital were analyzed for LPV–serum concentrations. They were then compared to those of 22 blood samples from out-patient children. Serum-level measurements were performed with an established high-performance liquid chromatography method. All LPV–serum levels of ICU patients were higher than a recommended Ctrough (= 1.000 ng/ml), 60% of levels were higher than Cmax (8.200 ng/ml). Partly, serum levels reached were extremely high (Maximum: 28.778 ng/ml). Low bodyweight and age correlated significantly with high LPV concentrations and were risk factors for serum levels higher than Cmax. Significantly fewer serum levels from infants in ICU care (mean: 11.552 ng/ml ± SD 7760 ng/ml) than from out-patient children (mean: 6.756 ng/ml ± SD 6.003 ng/ml) were subtherapeutic (0 vs. 28%, p = 0.008). Under total adherence in the ICU group, there were no subtherapeutic serum levels, while, in out-patient, children with unknown adherence 28% of serum levels were found subtherapeutic. Low bodyweight and age are risk factors for reaching potentially toxic LPV levels in this extremely fragile population. TDM can be a reasonable tool to secure sufficient and safe drug exposure in pediatric cART.


Therapeutic drug monitoring HIV Infectious diseases Pediatric intensive care Pediatric HIV care Infant HIV care Lopinavir Drug adherence 



Lots of gratitude to the doctors and nurses of the Pediatric Intensive Care Unit Ward A9 of Tygerberg Hospital, Cape Town, who lost their beloved consultant Dr. Louis Heynes to violent crime during the course of this investigation.

Compliance with ethical standards

Conflict of interest

The author has no conflicts of interest to declare.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Michael Schultheiß
    • 1
    Email author
  • Sharon Kling
    • 2
  • Ulrike Lenker
    • 1
  • Miriam von Bibra
    • 1
  • Bernd Rosenkranz
    • 3
  • Hartwig Klinker
    • 1
  1. 1.Medizinische Klinik und Poliklinik II, Schwerpunkt InfektiologieUniversitätsklinikum WürzburgWürzburgGermany
  2. 2.Department of Pediatrics and Child Health, Ward A9, Tygerberg HospitalUniversity of StellenboschTygerbergSouth Africa
  3. 3.Division of Clinical Pharmacology, Department of Medicine, Tygerberg HospitalUniversity of StellenboschTygerbergSouth Africa

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