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

• Published in: European journal of clinical pharmacology 1983, Vol.24 (2), p.267-271
• Main Authors: Aarbakke, J, Opshaug, O, Digranes, A, Høylandskjaer, A, Fluge, G, Fellner, H
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents, Urinary - therapeutic use; Bacteria - drug effects; Child, Preschool; Drug Combinations - metabolism; Drug Combinations - therapeutic use; Female; Humans; Infant; Kinetics; Male; Microbial Sensitivity Tests; Sulfadiazine - metabolism; Sulfadiazine - therapeutic use; Trimethoprim - metabolism; Trimethoprim - therapeutic use; Urinary Tract Infections - drug therapy; Urinary Tract Infections - metabolism
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00613830

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 micrograms/ml and 27 micrograms/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.