Pharmacokinetic Study of a New Derivative of Sulfamethoxazole

Abstract

The study was aimed at determination of phar macokinetic parameters of a previously syn thesized salicylidine-sulfamethoxazole-Zn(II) monohydrate in normal humans. This new deriv ative 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 col lected 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 adminis tration of the drug. The plasma samples were analyzed for sulfamethoxazole by a new vali dated high performance liquid chromatography method having a suitable limit of quantifi cation. The dose of each drug was well tolerated without any adverse eff ect. The maximum plasma sul famethoxazole concentration was 280 μg L − 1 at a t max 1.30 h. This suggests a rapid onset eff ect of the complex as compared with the parent drug. The plasma half-life, clearance, and volume of distribution of sulfamethoxazole from salicylid ine-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 fi rst order kinetics with R 2 > 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 eff ect with rapid clearance