Pharmacokinetic study of two sulfamethoxazole-phytochemical antimicrobial conjugates in mice.

Abstract

Antimicrobial resistance (AMR) has emerged to be a big threat to both human and animal health. Along the tighter control on antibiotic use, developing novel therapeutic agents and approaches is crucial for combating AMR. We recently designed and synthesized several antibiotic-phytochemical conjugates which exhibited potent antimicrobial activities. To understand their pharmacological behavior and obtain a guideline for further drug development, we undertook a pharmacokinetic study on sulfamethoxazole-gallate and sulfamethoxazole-caffeate. C_max was determined to be 842 ± 544 ng/mL at dose of 1500 mg/kg and 733 ± 477 ng/mL at dose of 2000 mg/kg for sulfamethoxazole-gallate and 211 ± 100 at a dose of 150 mg/kg and 755 ± 705 ng/mL at dose of 300 mg/kg for sulfamethoxazole-caffeate. T_max was 1 h for sulfamethoxazole-gallate under both doses and 0.5 h for sulfamethoxazole-caffeate under both doses. Since C_max was significantly lower than the in vitro MIC for both conjugates, more formulations and administration routes such as IV injection will be investigated in our future studies.