Pharmacokinetics and clinical experiences of sulfadiazine in low doses alone and in combination with trimethoprim
Seppänen, J.
Annals of Clinical Research 1980(25): 4-18
1980
ISSN/ISBN: 0003-4762 PMID: 7377749 Document Number: 162485
The pharmacokinetics of low doses of sulfadiazine was investigated in adults and children and in patients with renal failure of various degree. The pharmacokinetics, tissue penetration and synergistic antibacterial interaction of a combination of low dose sulfadiazine and trimethoprim was studied. The efficacy of the low doses of sulfadiazine alone in adults and children and in combination with trimethoprim in the treatment of acute urinary tract infections was evaluated. With sulfadiazine dosages of 500 mg once or twice daily and 250 mg twice daily alone or in combination with trimethoprim sufficient bacteriostatic concentrations were obtained in serum and urine for the treatment of acute urinary tract infections in adult patients with normal renal function. In children 4 mg/kg twice daily and in adults with renal failure 500 mg once daily gave effective drug levels in the serum and urine. Treatment of acute urinary tract infections with reduced doses of sulfadiazine (for adults 250 or 500 mg twice daily and for children 4 mg/kg twice daily) is comparable to with sulfonamides. A dose of 500 mg once daily can be continued for 1 wk in moderate and severe uremia without danger of toxic acumulation and side effects. Sulfadiazine and trimethoprim in combination (250 mg + 160 mg twice daily) apparently have a synergistic antibacterial interaction in the serum, urine, prostate gland, epididymis and testis in man; the combination is effective in the treatment of acute urinary tract infections and infections in these organs. With low doses of sulfadiazine there should be no danger of crystallization of the drug in the urinary tract regardless of the age of the patient or the state of renal function. Such pharmacokinetic properties of sulfadiazine as a relatively low degree of binding to plasma proteins and of metabolization make it possible to obtain sufficient drug concentrations in serum and urine, adequate penetration into tissues and good treatment results with much lower doses than previously used.