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

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie, Universitätsklinikum Würzburg, ZIM Haus A3/A4, Oberdürrbacher Str. 6, 97080, Würzburg, Germany

    Michael Schultheiß, Ulrike Lenker, Miriam von Bibra & Hartwig Klinker

  2. Department of Pediatrics and Child Health, Ward A9, Tygerberg Hospital, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa

    Sharon Kling

  3. Division of Clinical Pharmacology, Department of Medicine, Tygerberg Hospital, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa

    Bernd Rosenkranz

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  1. Michael Schultheiß
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  2. Sharon Kling
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  3. Ulrike Lenker
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  4. Miriam von Bibra
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Correspondence to Michael Schultheiß.

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Schultheiß, M., Kling, S., Lenker, U. et al. Lopinavir serum concentrations of critically ill infants: a pharmacokinetic investigation in South Africa. Med Microbiol Immunol 207, 339–343 (2018). https://doi.org/10.1007/s00430-018-0550-5

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  • DOI: https://doi.org/10.1007/s00430-018-0550-5

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