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Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections

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Summary

The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2–56 months. A suspension of TMP-SD (9+41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9–3.7 mg/kg/day) and SD (12.9–16.7 mg/kg/day) were also given to children of different ages. After 2–4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 µg/ml and 27 µg/ml, respectively, were found within 2–4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.

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Author notes

  1. J. Aarbakke

    Present address: Department of Pharmacology, Institute of Medical Biology, University of Tromsø, N-9001, Tromsø, Norway

Authors and Affiliations

  1. Department of Pharmacology, Gade Institute, University of Bergen, Bergen, Norway

    J. Aarbakke & A. Høylandskjær

  2. Department of Pediatrics, Gade Institute, University of Bergen, Bergen, Norway

    O. Opshaug & G. Fluge

  3. Department of Microbiology and Immunology, Gade Institute, University of Bergen, Bergen, Norway

    A. Digranes

  4. AB Astra, Sødertälje, Sweden

    H. Fellner

Authors
  1. J. Aarbakke
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  2. O. Opshaug
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  3. A. Digranes
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  4. A. Høylandskjær
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  5. G. Fluge
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  6. H. Fellner
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Aarbakke, J., Opshaug, O., Digranes, A. et al. Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections. Eur J Clin Pharmacol 24, 267–271 (1983). https://doi.org/10.1007/BF00613830

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  • DOI: https://doi.org/10.1007/BF00613830

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