Pharmacokinetics and clinical experiences of the combination sulfadiazine-trimethoprim in the short-term treatment of acute urinary tract infections.
The pharmacokinetics of sulfadiazine (SD) combined in a small dose (250 mg) with trimethoprim (TMP, 160 mg) and given twice daily were studied in eight healthy subjects. Both drugs were rapidly absorbed from the gastrointestinal tract and their concentrations in serum as well as in urine could be considered high enough for the treatment of acute urinary tract infections (UTI). In none of the subjects did the concentration of SD in urine exceed the experimental limit established for crystallization of the drug. Serum half-lives of SD and TMP were 10.8 and 11.8 hrs, respectively. In microbiological assay synergistic interaction was found in human urine with both the combination of SD + TMP and SM (sulfamethoxazole) + TMP on all the tested strains of E. coli, Str. faecalis, Str. agalactiae, Klebsiella pneumoniae and Proteus mirabilis. A double-blind clinical trial was carried out with patients having acute UTI, using either the combination SD + TMP (250 mg + 160 mg) or the combination SM + TMP (800 mg + 160 mg) twice daily for one week. The results of the treatment were equally successful in both groups. Treatment failed in only 4 out of 85 cases, although in 12 cases the causative micro-organism was resistant in vitro to the combination of SM + TMP.
D000208:Acute Disease; D000328:Adult; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008826:Microbial Sensitivity Tests; D013291:Streptococcus / Q000187:drug effects; D013411:Sulfadiazine / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D013420:Sulfamethoxazole / Q000627:therapeutic use; D013997:Time Factors; D014295:Trimethoprim / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000150:complications / Q000188:drug therapy*
D013411:Sulfadiazine; D014295:Trimethoprim; D013420:Sulfamethoxazole