{
  "abstract": "BackgroundSevere community-acquired pneumonia (CAP) remains a leading cause of mortality in children under five. The PediCAP trial evaluated oral step-down therapy using dispersible amoxicillin or amoxicillin/clavulanate tablets in African children hospitalised with severe CAP. Dispersible tablet formulations are preferred in children; however, pharmacokinetic data for oral amoxicillin/clavulanate in paediatric populations remain limited. We characterised the pharmacokinetics of 4:1, 7:1, and 14:1 dispersible amoxicillin/clavulanate tablets in children enrolled in the PediCAP trial and predicted target attainment under different dosing schemes.\n\nMethodsChildren were randomised within 24 hours of starting intravenous antibiotics to oral step-down therapy with weight-banded dosing of twice-daily amoxicillin/clavulanate (4:1, 7:1, or 14:1). Plasma concentrations were quantified following intensive sampling and analysed using nonlinear mixed-effects modelling with allometric scaling and postmenstrual age-dependent clearance maturation. Pharmacodynamic indices included %fT>MIC for amoxicillin and %fT>Ct for clavulanate.\n\nResultsA total of 157 children (median [range] age, 12 [2-70] months; weight, 8.4 [4.0-22.0] kg) contributed 707 paired concentrations. Amoxicillin was described by a two-compartment model and clavulanate by a one-compartment model, both with sequential zero-and first-order absorption. Typical clearance for an 8-kg individual at full maturation was 11.8L/h for amoxicillin and 6.1L/h for clavulanate. Pharmacokinetics were similar between the formulation ratios. Weight-banded dosing achieved balanced exposures across weight groups. Amoxicillin achieved 40%fT>MIC for MICs[≤]2mg/L. A proposed clavulanate target of 20%fT>0.5mg/L was achieved in most children even at the lowest amoxicillin/clavulanate ratio.\n\nConclusionWeight-banded dosing using dispersible amoxicillin/clavulanate tablets provide consistent exposure profiles in African children with severe CAP.\n\nSUMMARYPopulation pharmacokinetic modelling of dispersible amoxicillin/clavulanate tablets (4:1, 7:1, 14:1) in 157 African children with severe pneumonia showed weight-banded dosing achieved consistent and adequate amoxicillin and clavulanate exposures across formulations.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. van Dyk"
    },
    {
      "name": "M. S. Gebreyesus"
    },
    {
      "name": "M. Clements"
    },
    {
      "name": "J. Standing"
    },
    {
      "name": "D. Moore"
    },
    {
      "name": "Z. Dangor"
    },
    {
      "name": "Z. Waggie"
    },
    {
      "name": "B. Spittle"
    },
    {
      "name": "V. Mulenga"
    },
    {
      "name": "C. Chabala"
    },
    {
      "name": "H. Mujuru"
    },
    {
      "name": "W. C. Buck"
    },
    {
      "name": "M. Sidat"
    },
    {
      "name": "J. Sacarlal"
    },
    {
      "name": "J. A. Bielicki"
    },
    {
      "name": "V. Musiime"
    },
    {
      "name": "H. Xu"
    },
    {
      "name": "S. A. Madhi"
    },
    {
      "name": "M. Sharland"
    },
    {
      "name": "P. Denti"
    },
    {
      "name": "R. E. Wasmann"
    },
    {
      "name": "MRCCTU PediCAP"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9tewsymsrtgnz.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.26362138",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.18.26362138v1.full",
  "id": "9tewsymsrtgnz",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.18.26362138v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "pediatrics"
    ],
    [
      "openalex",
      "2736|Antibiotics Pharmacokinetics and Efficacy"
    ]
  ],
  "openalex": "W7214110634",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.18.26362138v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9tewsymsrtgnz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.64898/2026.09.18.26362138",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.18.26362138v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:pediatrics",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Population pharmacokinetics of child-friendly dispersible amoxicillin/clavulanate tablets in African children with severe community acquired pneumonia",
  "title_text": "Population pharmacokinetics of child-friendly dispersible amoxicillin/clavulanate tablets in African children with severe community acquired pneumonia",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/9tewsymsrtgnz",
  "venue": "medRxiv",
  "versions": []
}