Kaltenbach G, Levêque D, Peter J D, Salmon J, Elkhaili H, Cavalier A, Salmon Y, Monteil H, Jehl F
Institut de Bactériologie, Laboratoire de Pharmacocinétique, Strasbourg, France.
Pathol Biol (Paris). 1996 May;44(5):379-83.
The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. The pits received daily during three weeks oral itraconazole at a dosage of 200 mg at the beginning of the meal, then during the next two weeks oral itraconazole combined with an intravenous administration of rifampin at a dosage of 10 mg/kg/day. The coadministration of rifampin resulted in a 18 fold decrease of the Cmax of itraconazole [from 113.0 (SD: 17.2) to 6.2 ng/ml (SD: 3.9)], and in a 22 fold decrease of the AUC [from 1652.7 (SD: 297.7) to 75.6 ng.h/ml (SD: 30.01)]. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin considerably affects itraconazole kinetics at steady-state in this model of micropig, probably by inducing the hepatic metabolism of itraconazole.
本研究的目的是在三只尤卡坦小型猪体内，考察稳态下利福平对伊曲康唑药代动力学的影响。在为期三周的时间里，这些猪在每餐开始时每日口服200 mg伊曲康唑，然后在接下来的两周内口服伊曲康唑并静脉注射利福平，剂量为10 mg/kg/天。利福平的共同给药导致伊曲康唑的Cmax降低了18倍[从113.0（标准差：17.2）降至6.2 ng/ml（标准差：3.9）]，AUC降低了22倍[从1652.7（标准差：297.7）降至75.6 ng·h/ml（标准差：30.01）]。伊曲康唑的活性代谢产物羟基伊曲康唑未被检测到。本研究表明，在该小型猪模型中，利福平在稳态下会显著影响伊曲康唑的动力学，可能是通过诱导伊曲康唑的肝脏代谢。
