基于伏立康唑血药浓度监测的药物相互作用研究

The study on drug interactions based on therapeutic drug monitoring of voriconazole

目的临床药师通过治疗药物监测(TDM)手段,研究利福平和伏立康唑之间的药物相互作用。方法基于利福平和伏立康唑联用,及停用利福平后使用伏立康唑这两类患者的伏立康唑血药浓度监测情况,揭示利福平和伏立康唑间的药物相互作用强度与持续时间。结果18例利福平和伏立康唑联用患者,94.44%患者的伏立康唑血药浓度低于有效治疗浓度范围下限(1.0mg/L),其中72.22%患者低于定量下限0.16mg/L;19例停用利福平后再使用伏立康唑的标本中,停药6d内伏立康唑血药浓度小于1.0mg/L共12例,占总例数的63.16%,占停药6d内例数的91.67%;停药7d及以上伏立康唑血药浓度大于1mg/L的5例,占总例数的26.32%,占停药7d及以上例数的83.33%。结论利福平会严重降低伏立康唑血药浓度,在停用利福平第7d起伏立康唑血药浓度很可能才上升有效浓度范围,因此临床上应避免伏立康唑与利福平联用。临床药师借助TDM成功干预了有临床意义的药物相互作用,TDM是临床药师参与药物治疗的有效技术手段。

Objective Clinical pharmacists studied drug interactions between rifampicin and voriconazole by therapeutic drug monitoring (TDM). Methods The drug interactions between rifampicin and voriconazole were revealed based on the monitoring of serum concentrations of voriconazole in patients with rifampicin and after the discontinuation of rifampicin. Results In 18 patients with rifampicin combined with voriconazole, the voriconazole serum concentrations of 94.44% of patients were lower than the limit of effective treatment concentration (1.0mg/L), of which 72.22% were lower than the quantitative limit of 0.16mg/L. Among the 19 cases of patients who used voriconazole after rifampin was discontinued, the variconazole serum concentrations of 12 patients were less than 1.0mg/L within six days of discontinuation, accounting for 63.16% of the total cases and 91.67% of the six-day cases. The variconazole serum concentrations of five patients were greater than 1mg/L for seven days and above after rifampicin was discontinued, accounting for 26.32% of the total cases and 83.33% of the cases of seven days and above. Conclusion Rifampicin seriously reduced the serum concentrations of voriconazole, and it is very likely that the voriconazole serum concentrations increased into the effective concentration range after discontinuation of rifampicin on the seventh day, and thus the combination of voriconazole and rifampicin should be avoided in clinical practice. With the help of TDM, clinical pharmacists successfully interfered with clinically meaningful drug interactions. TDM is an effective technique for clinical pharmacists to participate in drug therapy.