头孢克洛与溴己新在中国健康人体内药动学环节的相互作用(英文)

Pharmacokinetic interaction between cefaclor and bromhexine in healthy Chinese volunteers

目的:研究头孢克洛和溴己新在中国健康成人体内药动学环节的相互作用。方法:采用3×3拉丁方试验设计,12名健康受试者在不同周期内分别多剂量口服头孢克洛片、盐酸溴己新片或头孢克洛片加盐酸溴己新片,周期间洗脱时间( Wash-out)为14 d。血及尿样中头孢克洛浓度采用HPLC-UV法测定,溴己新浓度采用HPLC-MS法测定。结果:将合并给予头孢克洛及溴己新组与单独给予头孢克洛组的主要药动学参数进行比较。头孢克洛的Cmax,AUC0-6(梯形面积)经对数转化后进行方差分析,结果表明二者均无统计学差异,双单侧t检验表明,两参数均落在各自相应的90%可信区间内,合用与单独使用相比,头孢克洛生物等效。tmax经Mann-Whitney检验,结果表明两组间无统计学差异。其他药动学参数(如:Vd/F,t1/2,Clr及MRT等)进行方差分析,结果显示:Vd/F有统计学差异,其他参数无统计学差异。将合并给予头孢克洛和溴己新组与单独给予溴己新组的主要药动学参数进行比较。溴己新的主要药动学参数Cmax,AUC0-24(梯形面积)经对数转化后进行方差分析,结果表明二者无统计学差异,双单侧t检验表明,两参数均落在各自相应的90%可信区间内,合用与单独使用相比,溴己新生物等效。tmax经Mann-Whitney检验,结果表明无统计学差异。其他药动学参数(如:Vd/F,t1/2,Clr及MRT)进行方差分析,参数均无统计学差异。结论:联合服用盐酸溴己新片与头孢克洛,药物的吸收、代谢及排泄不受影响;头孢克洛的表观分布容积高于单用头孢克洛,这可能是两药药效学协同作用的药动学基础。

Objective To determine the pharmacokinetic interaction between cefalor and brom- hexine in healthy Chinese volunteers. Methods Twelve subjects received a cefaclor （CEF） treat- ment, a bromhexine （BHX） treatment, and a cotreatment of CEF and BHX with a 3×3 Latin square design. The wash-out time between periods was 14 days. The plasma and urine drug concen- trations of CEF and BHX were detected by HPLC-UV and LC/MS, respectively. Results All the 12 volunteers completed the study. There were no significant differences in AUC0-t and Cmax of CEF in logarithm between the single administration group of CEF and the coadministration group of CEF with BHX. Two one sided ttest showed that CEF was bioequivalent in the 2 groups. There were no significant differences in t MRT, tl/2, and Clr between the 2 groups. Vd/F was significantly lower in the single CEF group than in the coadministration group of CEF and BHX. There were no significant differences of AUC0-t, and Cmax of BHX in logarithm between the single administration group of BHX and the coadministration group of BHX with CEF. Two one sided t-test showed that BHX was bioequivalent in the 2 groups. There were no significant differences in t MRT, tl/2, Vd/F, and C1r between the 2 groups. Conclusion There is no significant pharmacokinetic parameter change in the drug absorption, metabolism, and excretion, but Vd/F of CEF significant increases in the coad- ministration of CEF with BHX. The co-administration of CEF and BHX has no adverse drug interaction. The increase of Vd/F may be a favorable drug interaction, which may be the mechanism of the synergistic effect of the 2 drugs.