Sulfonamide and trimethoprim concentrations in human serum and skin blister fluid

Abstract

Various sulfonamides and trimethoprim were given orally twice a day to healthy volunteers. The drug concentrations in serum and tissue fluid from skin blisters were determined concomitantly. Maximal serum concentrations were obtained after 1 to 3 h. Absorption of sulfacarbamide and sulfadimidine was more rapid than for sulfadiazine, sulfamethoxazole, and trimethoprim. The penetration to blister fluid was delayed and mimal concentrations were usually reached after 4 to 8 h. The highest penetration to blister fluid was found for sulfacarbamide, sulfadiazine, and trimethoprim. During maintenance therapy sulfadiazine and trimethoprim gave blister fluid concentrations usually above 50% of the serum level. However, on the basis of dosage the highest sulfonamide concentration both in serum and blister fluid was obtained with sulfamethoxazole.

Anti-fungal Activity of Sulfamethoxazole toward Aspergillus Species

“…Therefore, the concentration of 100 mg/ml may be a little high level, but actually it can be this concentration. 33,34) Furthermore, we have shown that the anti-fungal effect depends on not TMP but SMX and that it is inhibited by PABA which antagonizes SMX. Those results suggested that SMX-TMP used as a bactericidal agent has not only an anti-bacterial effect but also an anti-fungal one.…”

Pharmacokinetics of Methioprim in Human Volunteers

“…The observed increase in serum creatinine corresponds to a similar reversible in crease observed during trimethoprim ther apy and is at least partly thought to be re lated to inhibition of the tubular secretion of creatinine [3].…”

Human Pharmacokinetics and Skin Blister Levels of Sulfonamides and Dihydrofolate Reductase Inhibitors

“…Although this practice has been supported by moni toring serum levels, the present blister data demonstrate that higher loading doses also produce desirable high extravascular levels closer to where the infec tious microbes would be lodged. The pro tein level in our blister fluid has shown a slight increase from early to 12-hour-old blisters, and the protein content is also somewhat higher than in interstitial fluid [2]. This and the experimental aspects of this model may challenge the relevance of our skin blister model for extravascular foci in general, but the patterns produced by the suction blisters are reproducible, and such a technique thus constitutes a useful procedure for the study of penetra tion as was demonstrated by this study.…”

“…The skin blisters were produced by a perspex block with 8 circular holes of 0.8 cm diameter to which a negative pressure of 0.3 kg/cm2 was applied for 1.5-2 h until hemispherical blisters had devel oped, as described previously [2,5]. The blisters were made on one arm on the first day of the study and on the opposite arm on the 4th day.…”