Summary
Serum kinetics of trimethoprim and sulfamethoxazole were studied in 23 patients during oral and i.v. treatment ofPneumocystis carinii pneumonia. Daily doses of 15–22 mg/kg trimethoprim and 75–110 mg/kg sulfamethoxazole were given every 6 h. Despite administration of a loading dose of twice the regular dose, serum trough concentrations continuously rose from 12 h to 96 h by 63% for trimethoprim and 102% for sulfamethoxazole. After 4–6 days mean trough concentrations of trimethoprim and sulfamethoxazole were 7.7 ± 3.0 and 198 ± 74 mg/l, with individual values of < 4.6 and < 103 mg/l in two patients and > 11.4 and > 307 mg/l in two others. Patients treated orally or i. v. had similar serum levels. However, large interindividual variability was observed despite weight-specific dosing. Administration of a loading dose did not prevent accumulation of serum levels of trimethoprim and sulfamethoxazole over several days of treatment.
Zusammenfassung
Die Serumkinetik von Trimethoprim und Sulfamethoxazol wurde bei 23 Patienten während oraler oder parenteraler Behandlung vonPneumocystis carinii-Pneumonien untersucht. Tagesdosen von 15–22 mg/kg Trimethoprim und 75–110 mg/kg Sulfamethoxazol wurden in Intervallen von 6 Stunden verabreicht. Trotz der Verabreichung von Ladungsdosen, die dem Zweifachen der Einzeldosen entsprachen, stiegen die Talspiegel im Serum zwischen 12 und 96 h bei Trimethoprim um 63% und bei Sulfamethoxazol um 102% an. Nach 4 bis 6 Tagen betrugen die mittleren Talkonzentrationen bei Trimethoprim 7.7 ± 3.0 und bei Sulfamethoxazol 198 ± 74 mg/l, mit-Einzelwerten von < 4.6 und < 103 mg/l Trimethoprim sowie > 11.4 und > 307 mg/l Sulfamethoxazol bei je zwei Patienten. Trotz gewichtsspezifischer Dosierung wurde eine große interindividuelle Variabilität beobachtet. Oral und parenteral behandelte Patienten wiesen vergleichbare Konzentrationen auf. Die Verabreichung der Ladungsdosen konnte eine Akkumulation von Trimethoprim und Sulfamethoxazol während der ersten Tage der Behandlung nicht verhindern.
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Blaser, J., Joos, B., Opravil, M. et al. Variability of serum concentrations of trimethoprim and sulfamethoxazole during high dose therapy. Infection 21, 206–209 (1993). https://doi.org/10.1007/BF01728888
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DOI: https://doi.org/10.1007/BF01728888