不同磺胺类药物对人体苯妥英代谢的影响。

The effect of different sulfonamides on phenytoin metabolism in man.

作者信息

Hansen J M, Kampmann J P, Siersbaek-Nielsen K, Lumholtz I B, Arrøe M, Abildgaard U, Skovsted L

出版信息

Acta Med Scand Suppl. 1979;624:106-10. doi: 10.1111/j.0954-6820.1979.tb00729.x.

DOI:10.1111/j.0954-6820.1979.tb00729.x

Abstract

The influence on the metabolism of phenytoin of some sulfonamides given in common clinical doses has been studied. In single dose experiments sulfaphenazole increased phenytoin half-life (T/2) by 237% and decreased phenytoin metabolic clearance rate (MCR) by 67%. Sulfadiazine, sulfamethiazole, sulfamethoxazole + trimethoprim and trimethoprim increased phenytoin T/2 by 80, 66, 39 and 51% respectively, and decreased phenytoin MCR by 45, 36, 27 and 30% respectively. Sulfamethoxazole gave a small but significant increase in phenytoin T/2 but not a corresponding fall in phenytoin MCR. No changes were found in phenytoin T/2 and MCR after treatment with sulfamethoxypyridazine, sulfadimethoxine and sulfamethoxydiazine. Steady state experiments confirmed the findings of the single dose experiments. It is suggested that sulfaphenazole, sulfadiazine, sulfamethizole, sulfamethoxazole + trimethoprim and trimethoprim inhibit hepatic metabolism of phenytoin.

摘要

研究了一些临床常用剂量的磺胺类药物对苯妥英代谢的影响。在单剂量实验中，磺胺苯吡唑使苯妥英半衰期（T/2）增加了237%，并使苯妥英代谢清除率（MCR）降低了67%。磺胺嘧啶、磺胺甲噻二唑、磺胺甲恶唑+甲氧苄啶和甲氧苄啶分别使苯妥英T/2增加了80%、66%、39%和51%，并分别使苯妥英MCR降低了45%、36%、27%和30%。磺胺甲恶唑使苯妥英T/2有小幅但显著的增加，但苯妥英MCR没有相应下降。服用磺胺甲氧嗪、磺胺二甲氧嘧啶和磺胺甲氧哒嗪后，苯妥英T/2和MCR未发现变化。稳态实验证实了单剂量实验的结果。提示磺胺苯吡唑、磺胺嘧啶、磺胺甲噻二唑、磺胺甲恶唑+甲氧苄啶和甲氧苄啶抑制苯妥英的肝脏代谢。