Sun Jianguo, Wang Zhipeng, Liu Na, Liu Zhijun, Cui Lili, Tao Xia, Chen Wansheng, Gao Shouhong, Wu Zhijun
Department of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai, China.
College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, China.
Front Pharmacol. 2024 May 23;15:1344369. doi: 10.3389/fphar.2024.1344369. eCollection 2024.
Tacrolimus (Tac) is commonly used for postoperative immunosuppressive therapy in transplant patients. However, problems, for example, low bioavailability and unstable plasma concentration, persist for a long time, Studies have reported that the deoxyschizandrin could effectively improve these problems, but the pharmacokinetic parameters (PKs) of Tac combined with deoxyschizandrin are still unknown.
In this study, an UHPLC-MS/MS method has been established for simultaneous quantitation of Tac and deoxyschizandrin. The PKs of Tac influenced by different doses of deoxyschizandrin after single and multiple administrations were analyzed, and the different impact of deoxyschizandrin and Wuzhi capsule on PKs of Tac were compared.
The modified UHPLC-MS/MS method could rapid quantification of Tac and deoxyschizandrin within 2 min using bifendatatum as the internal standard (IS). All items were successfully validated. The of deoxyschizandrin increased from 148.27 ± 23.20 to 229.13 ± 54.77 ng/mL in rats after multiple administrations for 12 days. After co-administration of 150 mg/mL deoxyschizandrin, Tac had an earlier and greater and AUC, and the and AUC of Tac increased from 14.26 ± 4.73 to 54.48 ± 14.37 ng/mL and from 95.10 ± 32.61 to 315.23 ± 92.22 h/ng/mL, respectively; this relationship was positively proportional to the dosage of deoxyschizandrin. In addition, compared with Wuzhi capsule, the same dose of deoxyschizandrin has a better effective on Tac along with more stable overall PKs.
An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.
他克莫司（Tac）常用于移植患者的术后免疫抑制治疗。然而，诸如生物利用度低和血浆浓度不稳定等问题长期存在。研究报道，五味子醇甲可有效改善这些问题，但Tac与五味子醇甲联合应用时的药代动力学参数（PKs）仍不清楚。
本研究建立了一种超高效液相色谱-串联质谱（UHPLC-MS/MS）法，用于同时定量测定Tac和五味子醇甲。分析单次及多次给药后不同剂量五味子醇甲对Tac药代动力学的影响，并比较五味子醇甲和五酯胶囊对Tac药代动力学的不同影响。
采用联苯双酯作为内标（IS），改良的UHPLC-MS/MS法可在2分钟内快速定量测定Tac和五味子醇甲。所有项目均成功验证。多次给药12天后，大鼠体内五味子醇甲的浓度从148.27±23.20 ng/mL增加到229.13±54.77 ng/mL。联合给予150 mg/mL五味子醇甲后，Tac的达峰时间更早，峰浓度和曲线下面积（AUC）更大，Tac的峰浓度和AUC分别从14.26±4.73 ng/mL增加到54.48±14.37 ng/mL，从95.10±32.61 h/ng/mL增加到315.23±92.22 h/ng/mL；这种关系与五味子醇甲的剂量成正比。此外，与五酯胶囊相比，相同剂量的五味子醇甲对Tac的疗效更好，整体药代动力学更稳定。
建立并验证了一种UHPLC-MS/MS法，用于同时检测五味子醇甲和Tac。五味子醇甲可提高Tac的暴露水平和稳定性，此外，在相同剂量下，其效果优于五酯胶囊。
