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Aim: A sensitive and reliable LC–MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug–drug interactions occurred between RIV and TAK-438 when co-administered to rats.

Aim: A reliable, sensitive and simple LC–MS/MS method has been established and validated for the quantitation of rivaroxaban (RIV) and metformin (MET) in rat plasma. Results: The procedure of method validation was conducted according to the guiding principles of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and MET for the first time. When RIV and MET coadministered to rats, pharmacokinetic parameters of MET like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increased. tmax of RIV was prolonged without affecting t1/2 obviously and Cmax was inhibited significantly (p < 0.05) by comparison to the single group. Conclusion: The results indicated that drug–drug interactions occurred when the coadministration of RIV and MET.

Background Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are two famous herbs and often used in many traditional Chinese compound prescriptions. In clinical practice, ACW-SBG couple as a famous traditional herb couple, was widely used for treating infantile cough, phlegm and fever which caused by pulmonary infection. Meanwhile, a standardized bioflavonoid composition-UP446 with ACW extract and SBG extract has been used in both special nutritional products and joint care dietary supplements. However, its herb-herb interactions based on absorption, distribution, metabolism and excretion (ADME) study had not been investigated. Purpose The aim of this study was to evaluate potential pharmacokinetic, tissue distribution and excretion interactions between ACW and SBG, and to provide useful information for the development of suitable dosage forms and clinical applications. Study design and methods A sensitive and reliable LC-MS/MS method was established to the quantification of four major bioactive components in rat biological samples. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. Based on this, we obtained and compared the parameters about pharmacokinetics, tissue distribution and excretion of four major bioactive components in this study. Results This work revealed that the parameters including plasma pharmacokinetics, tissue distribution and excretion of (+)-catechin (C), (-)-epicatechin (EC), baicalin (BL) and baicalein (BLE) in single administration had significant differences compared co-administration. The results illustrated that interactions between two herbs are related to the effect of competitive gastrointestinal absorption inhibition and drug metabolism by liver metabolic enzymes. Moreover, the alteration of C and EC in the tissue of lung maybe could enhance the pharmacological activity for treating pulmonary infection. Conclusion This is the first report to evaluate the pharmacokinetics, tissue distribution and excretion of co-administration of ACW or SBG to rats and compared its properties of four major bioactive components. The results demonstrate that herb –herb interactions occurred in this herb couple.