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  • Title: Pharmacokinetics of sulfadiazine and trimethoprim in man.
    Author: Andreasen F, Elsborg L, Husted S, Thomsen O.
    Journal: Eur J Clin Pharmacol; 1978 Nov 09; 14(1):57-67. PubMed ID: 729608.
    Abstract:
    Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual "peak" concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 microgram/ml for SDZ and 0.3 to 1.1 microgram/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h)--145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 microgram/ml for SDZ and from 13.8 to 93.4 microgram/ml for TMP. The fraction (formula: see text) was 21% during the 0--8 h period, 33% during the 8--15 h period and 41% during the 15--24 period. The average "t1/2" was 15.2 +/- 7.4 h for SDZ and 7.4 +/- 1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p less than 0.01) and also between the renal clearance of the two drugs (p less than 0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ Vd was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for "acetylated SDZ". The renal clearance of "acetylated SDZ" averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.
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