Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Oliveira, Alexandre Cavenatti de; Davanço, Marcelo Gomes; Campos, Daniel Rossi de; Sanches, Pedro Henrique Godoy; Cirino, João Pedro Gonçalves; Carvalho, Patrícia de Oliveira; Antônio, Márcia Aparecida; Coelho, Emerson Filipino; Porcari, Andréia M.

doi:10.1002/bmc.5147

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…For rivaroxaban analysis, the LC-MS/MS method was implemented as described in the previous reports ( Wang et al, 2020 ; de Oliveira et al, 2021 ). In brief, the mobile phase consisted of solvent A (1 mM ammonium formate in water) and solvent B (0.1% formic acid in methanol) using gradient elution at a flow rate of 0.3 ml/min.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Wang

Zhang

et al. 2022

Front. Pharmacol.

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The combination of Salvia miltiorrhiza (Danshen) and rivaroxaban is a promising treatment option in clinical practice in China, but the herb–drug interaction between Danshen and rivaroxaban remains unclear. Therefore, this study aims to reveal the interaction between Danshen and rivaroxaban. We not only investigated the inhibitory properties of Danshen tablet on rivaroxaban metabolism in rat and human liver microsomes but also evaluated the inhibitory effects of Danshen tablet and its eight active components (dihydrotanshinone I, tanshinone I, tanshinone IIA, cryptotanshinone, danshensu, salvianolic acid A, salvianolic acid B, and salvianolic acid C) on cytochrome P450 (CYP) enzymes. The results showed that Danshen tablet potently inhibited the metabolism of rivaroxaban in rat and human liver microsomes. In the CYP inhibition study, we found that dihydrotanshinone I, the active component of Danshen tablet, potently inhibited the activities of rat CYP3A and CYP2J, with IC50 values at 13.85 and 6.39 μM, respectively. In further inhibition kinetic study, we found that Danshen tablet is a mixed inhibitor in rivaroxaban metabolism in rat and human liver microsomes, with the Ki value at 0.72 and 0.25 mg/ml, respectively. In conclusion, there is a potential interaction between Danshen tablet and rivaroxaban. Danshen tablet inhibits the metabolism of rivaroxaban, which may be because its lipid-soluble components such as dihydrotanshinone I strongly inhibit the activities of CYP enzymes, especially CYP3A and CYP2J. Therefore, when Danshen tablet and rivaroxaban are used simultaneously in the clinic, it is necessary to strengthen the drug monitoring of rivaroxaban and adjust the dosage.

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Section: Methodsmentioning

confidence: 99%

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Wang

Zhang

et al. 2022

Front. Pharmacol.

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“…11 Oliveira et al worked on LC-MS/MS instrument and developed sensitive method in plasma for quantification of RVB. 12 Alam et al established ecofriendly HPTLC method using green solvents in nanoparticle formulations for RVB estimation. 13 Shukla et al established HPTLC method in human plasma.…”

Section: Introductionmentioning

confidence: 99%

Validated Stability Indicating HPTLC Method Development for Rivaroxaban in Tablets

Nimje,

Magar,

Kamble

et al. 2024

Ind. J. Pharm. Edu. Res

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“…Several methods exist for determining the blood concentration of rivaroxaban and apixaban, but they each have limitations, such as a narrow range of calibration curves ( Lagoutte-Renosi et al, 2018 ; Dunois, 2021 ), a high volume of plasma required, tedious pre-processing steps, and the use of a large among of organic reagents ( de Oliveira et al, 2021 ; Zidekova et al, 2023 ). While a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is available for determining rivaroxaban and apixaban, it can not be used to quantify almonertinib under these conditions ( Zhang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Wang,

Li,

et al. 2023

Front. Pharmacol.

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Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment.Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR).Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

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Sensitive LC–MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies

Cited by 7 publications

References 28 publications

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Evaluation of Herb–Drug Interaction Between Danshen and Rivaroxaban in Rat and Human Liver Microsomes

Validated Stability Indicating HPTLC Method Development for Rivaroxaban in Tablets

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

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