Human pharmacokinetics and skin blister levels of sulfonamides and dihydrofolate reductase inhibitors

Abstract

The penetration into suction skin blisters and pharmacokinetics of 4 sulfonamides (sulfacarbamide, sulfadimidine, sulfadiazine, sulfamethoxazole) and two dihydrofolate reductase inhibitors (methioprim, trimethoprim) have been compared in healthy volunteers. The concentrations were monitored after the first dose and for the subsequent 4 days when approximate steady state conditions could be assumed to have been established. The serum or plasma half-life of the agents in the above order was 3.1, 6.3, 13.9, 12.1, 9.3, and 12.0 h. The respective areas under the serum curves were 97.1, 607.8, 942.6, 1423.1, 128.1 and 175.4 mg/l per dose of 1.0 g. With the sulfonamides, there was a distinct correlation between serum protein binding and pKa and the ability of the compounds to penetrate into blister fluid as shown by the 12-hour ratios between areas under the concentration curves in blister fluid relative to serum.