[Comparison of pharmacokinetics of the combination trimethoprim and sulfamethoxazole in patients with liver diseases and healthy persons].
Pharmacokinetic characteristics of the antibacterial combination sulfamethoxazole (SMZ) plus trimethoprim (TMP) have been compared, following a single oral dose of 800 mg SMZ plus 160 mg TMP, between 3 groups of adult humans: A = 13 healthy persons, B = 4 patients with minor hepatic injury and C = 7 patients with severe, decompensated liver damage. The following data were determined: 1. the time tmax; 2. the maximum concentrations (cmax) of the two drugs reached in the plasma; 3. the half-life t1/2 of their elimination from the plasma; 4. their apparent distribution volume indicated in percent of body weight; 5. the share of metabolized SMZ in percent of total sulfonamide; 6. the concentration ratio of active SMZ to TMP, both total and unbound to plasma proteins; 7. the cumulative renal excretion of total sulfonamide and of non-metabolized TMP. Only the following differences between groups were observed: 1. The maximum plasma level of active SMZ as well as TMP was lower by an average factor of 1.5 to 2.0 in the two groups B and C as compared to group A. An analogous but diminishing difference lasted for the active SMZ up to the 24th, for TMP up to the 12th hour following medication. An influence of the liver disease on the absorption rate via alteration of the biliary conditions is envisaged as a possible explanation. 2. The elimination half-life of TMP, although lying in most of the liver patients within the range of healthy persons, was lengthened up to twice normal in some of the patients with severe liver damage. Such unusually long half-lives for TMP, however, are considered to be in the range of an individual peculiarity. 3. The renal excretion of TMP occurred in the liver-diseased patients on the average more slowly during the first 24 h and its cumulative value reached at the end of the 72 h observation time was somewhat lower than in the healthy persons. In group C at least this may be in connection with a concomitant reduction of the kidney function. None of the features indicated are considered to be of essential clinical importance, such as to discourage the use of the combination in cases of liver disease.
D000328:Adult; D000368:Aged; D001835:Body Weight; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013420:Sulfamethoxazole / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D014295:Trimethoprim / Q000008:administration & dosage / Q000378:metabolism*
D004338:Drug Combinations; D014295:Trimethoprim; D013420:Sulfamethoxazole
Pharmakokinetik der Wirkstoffkombination Trimethoprim + Sulfamethoxazol bei Leberkranken im Vergleich zu Gesunden