Population pharmacokinetics of intramuscular artesunate in african children with severe malaria

Implications for a practical dosing regimen

Ilse Hendriksen, George Mtove, Alison Kent, Samwel Gesase, Hugh Reyburn, Martha Lemnge, Lindegardh, Nicholas Day, Lorenz Von Seidlein, Nicholas J White, Arjen Dondorp, J TARNING

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. � 2013 American Society for Clinical Pharmacology and Therapeutics.
    Original languageEnglish
    Pages (from-to)443-450
    Number of pages8
    JournalClinical Pharmacology and Therapeutics
    Volume93
    Issue number5
    Early online date8 Feb 2013
    DOIs
    Publication statusPublished - May 2013

    Fingerprint

    dihydroartemisinin
    Malaria
    Pharmacokinetics
    Population
    Falciparum Malaria
    Critical Illness
    artesunate
    Body Weight
    Weights and Measures
    Mortality
    Therapeutics
    Pharmaceutical Preparations

    Cite this

    Hendriksen, Ilse ; Mtove, George ; Kent, Alison ; Gesase, Samwel ; Reyburn, Hugh ; Lemnge, Martha ; Lindegardh ; Day, Nicholas ; Von Seidlein, Lorenz ; White, Nicholas J ; Dondorp, Arjen ; TARNING, J. / Population pharmacokinetics of intramuscular artesunate in african children with severe malaria : Implications for a practical dosing regimen. In: Clinical Pharmacology and Therapeutics. 2013 ; Vol. 93, No. 5. pp. 443-450.
    @article{bdaf10ce09b3436b904688b461518780,
    title = "Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: Implications for a practical dosing regimen",
    abstract = "Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. � 2013 American Society for Clinical Pharmacology and Therapeutics.",
    keywords = "amodiaquine, artemether plus benflumetol, artesunate, dihydroartemisinin, pyrimethamine plus sulfadoxine, quinine, area under the curve, article, body weight, child, disease severity, drug blood level, drug clearance, drug disposition, drug distribution, follow up, human, infant, major clinical study, malaria falciparum, maximum plasma concentration, pharmacodynamics, plasma concentration-time curve, preschool child, priority journal, school child, Tanzania, time to maximum plasma concentration, Antimalarials, Artemisinins, Body Weight, Child, Child, Preschool, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Infant, Injections, Intramuscular, Malaria, Falciparum, Models, Biological, Nonlinear Dynamics, Severity of Illness Index, Time Factors, Tissue Distribution",
    author = "Ilse Hendriksen and George Mtove and Alison Kent and Samwel Gesase and Hugh Reyburn and Martha Lemnge and Lindegardh and Nicholas Day and {Von Seidlein}, Lorenz and White, {Nicholas J} and Arjen Dondorp and J TARNING",
    year = "2013",
    month = "5",
    doi = "10.1038/clpt.2013.26",
    language = "English",
    volume = "93",
    pages = "443--450",
    journal = "Clinical Pharmacology and Therapeutics",
    issn = "0009-9236",
    publisher = "Mosby International",
    number = "5",

    }

    Hendriksen, I, Mtove, G, Kent, A, Gesase, S, Reyburn, H, Lemnge, M, Lindegardh, Day, N, Von Seidlein, L, White, NJ, Dondorp, A & TARNING, J 2013, 'Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: Implications for a practical dosing regimen', Clinical Pharmacology and Therapeutics, vol. 93, no. 5, pp. 443-450. https://doi.org/10.1038/clpt.2013.26

    Population pharmacokinetics of intramuscular artesunate in african children with severe malaria : Implications for a practical dosing regimen. / Hendriksen, Ilse; Mtove, George; Kent, Alison; Gesase, Samwel; Reyburn, Hugh; Lemnge, Martha; Lindegardh; Day, Nicholas; Von Seidlein, Lorenz; White, Nicholas J; Dondorp, Arjen; TARNING, J.

    In: Clinical Pharmacology and Therapeutics, Vol. 93, No. 5, 05.2013, p. 443-450.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Population pharmacokinetics of intramuscular artesunate in african children with severe malaria

    T2 - Implications for a practical dosing regimen

    AU - Hendriksen, Ilse

    AU - Mtove, George

    AU - Kent, Alison

    AU - Gesase, Samwel

    AU - Reyburn, Hugh

    AU - Lemnge, Martha

    AU - Lindegardh, null

    AU - Day, Nicholas

    AU - Von Seidlein, Lorenz

    AU - White, Nicholas J

    AU - Dondorp, Arjen

    AU - TARNING, J

    PY - 2013/5

    Y1 - 2013/5

    N2 - Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. � 2013 American Society for Clinical Pharmacology and Therapeutics.

    AB - Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. � 2013 American Society for Clinical Pharmacology and Therapeutics.

    KW - amodiaquine

    KW - artemether plus benflumetol

    KW - artesunate

    KW - dihydroartemisinin

    KW - pyrimethamine plus sulfadoxine

    KW - quinine

    KW - area under the curve

    KW - article

    KW - body weight

    KW - child

    KW - disease severity

    KW - drug blood level

    KW - drug clearance

    KW - drug disposition

    KW - drug distribution

    KW - follow up

    KW - human

    KW - infant

    KW - major clinical study

    KW - malaria falciparum

    KW - maximum plasma concentration

    KW - pharmacodynamics

    KW - plasma concentration-time curve

    KW - preschool child

    KW - priority journal

    KW - school child

    KW - Tanzania

    KW - time to maximum plasma concentration

    KW - Antimalarials

    KW - Artemisinins

    KW - Body Weight

    KW - Child

    KW - Child, Preschool

    KW - Dose-Response Relationship, Drug

    KW - Drug Administration Schedule

    KW - Humans

    KW - Infant

    KW - Injections, Intramuscular

    KW - Malaria, Falciparum

    KW - Models, Biological

    KW - Nonlinear Dynamics

    KW - Severity of Illness Index

    KW - Time Factors

    KW - Tissue Distribution

    U2 - 10.1038/clpt.2013.26

    DO - 10.1038/clpt.2013.26

    M3 - Article

    VL - 93

    SP - 443

    EP - 450

    JO - Clinical Pharmacology and Therapeutics

    JF - Clinical Pharmacology and Therapeutics

    SN - 0009-9236

    IS - 5

    ER -