增效联磺片的体外溶出度和体内生物利用度

建立了测定体外溶出介质中磺胺嘧啶(SD)、磺胺甲噁唑(SMZ)和甲氧苄啶(TMP)及血浆中SD,SMZ,TMP和两个代谢产物N⁴-acetyl-SD和N⁴-acetyl-SMZ的反相高效液相色谱法,并对市售两种增效联磺片(片剂A和B)进行了体外溶出度和人体内生物利用度的研究。体外溶出度实验表明:两种片剂相同主药的T⁵⁰差异非常显著(P<0.001),片剂A主药的溶出比B快。生物利用度试验表明:片剂B相对于A的口服吸收分数为0.73(SD),0.78(SMZ)和0.83(TMP),口服片剂后各主药的体内过程符合表观一级吸收和一级消除的单室模型。

STUDIES ON THE DISSOLUTION AND BIOAVAILABILITY OF TRIMETHOPRIM-SULFADIAZINE-SULFAMETHOXAZOLE TABLETS

A reverse- phase high performance liquid chromatographic method wasestablished for the simultaneous determination of trimethoprim (TMP), sulfadiazine (SD)and sulfamethoxazole (SMZ) in dissolution media. Meanwhile, another reverse- phasehigh performance liquid chromatographic method was developed for the simultaneous deter-mination of the three drugs mentioned above and their metabolites, N~4- acetyl - SD andN~4- acetyl-SMZ in serum. The in vitro dissolution and in vivo bioavailability of twocommercial trimethoprim- sulfadiazine- sulfamethoxazole tablets (A and B) werestudied. Drugs were released far more rapidly from A than from B. Significant difference(P<0.001)was observed between the T_(50) s of the same active principles released from Aand B. The in vivo processes of all three active principles in 8 healthy subjects taking twotablets each could be described by one- compartment model with first - order absorptionand elimination. Compared with A, the relative bioavailabilities of B were 0.83,0.73and 0.78 for TMP, SD and SMZ, respectively. Drugs were absorbed more rapidly fromA than from B.