Pharmacokinetic study of a new derivative of sulfamethoxazole.

Abstract

The study was aimed at determination of pharmacokinetic parameters of a previously synthesized salicylidine-sulfamethoxazole-Zn(II) monohydrate in normal humans. This new derivative of sulfamethoxazole was reported to be more active and less toxic than the parent drug by our group. 10 volunteers received a 200 mg dose of the drug orally. Blood samples were collected just before and after 0.16, 0.33, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0 h of administration of the drug. The plasma samples were analyzed for sulfamethoxazole by a new validated high performance liquid chromatography method having a suitable limit of quantification. The dose of each drug was well tolerated without any adverse effect. The maximum plasma sulfamethoxazole concentration was 280 μg L - 1 at a tmax 1.30 h. This suggests a rapid onset effect of the complex as compared with the parent drug. The plasma half-life, clearance, and volume of distribution of sulfamethoxazole from salicylidine-sulfamethoxazole-Zn(II) monohydrate were 1.64 h, 0.24 L h - 1 and 0.57 L kg - 1 respectively. The elimination of sulfamethoxazole followed the first order kinetics with R2>0.984. The larger value of volume of distribution and clearance for the new derivative, as compared to that of the parent drug, show that the new derivative may exhibit prolonged antimicrobial effect with rapid clearance.