AUTHOR=Sun Jianguo , Wang Zhipeng , Liu Na , Liu Zhijun , Cui Lili , Tao Xia , Chen Wansheng , Gao Shouhong , Wu Zhijun 

TITLE=Pharmacokinetic assessment of tacrolimus in combination with deoxyschizandrin in rats

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1344369

DOI=10.3389/fphar.2024.1344369

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Method</title><p>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.</p></sec><sec><title>Result</title><p>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 <italic>C</italic><sub>max</sub> 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 <italic>T</italic><sub>max</sub> and greater <italic>C</italic><sub>max</sub> and AUC<sub>0–t</sub>, and the <italic>C</italic><sub>max</sub> and AUC<sub>0–t</sub> 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.</p></sec><sec><title>Conclusion</title><p>An UHPLC-MS/MS method was established and validated for simultaneous detection of deoxyschizandrin and Tac. Deoxyschizandrin could improve the <italic>in vivo</italic> exposure level and stability of Tac, besides, this effect is better than Wuzhi capsule in same dose.</p></sec>