Ying Li’s research while affiliated with China Meitan General Hospital and other places

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Publications (33)


Effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in vivo
  • Article

December 2024

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1 Read

Journal of Chromatography B

Zhi Wang

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Zefang Yu

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Lingzhi Fang

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[...]

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Zhanjun Dong

Figure 5
Figure 6
Experimental setting for the tandem mass-spectrometer for the analytes and internal standards.
Pharmacokinetic parameters of donafenib in rats after oral administration alone and following multiple doses of empagliozin or henagliozim.
Pharmacokinetic parameters of empagliozin in rats after oral administration alone and following multiple doses of donafenib. Parameters (Unit) empagliozin (2.5 mg/kg)
Pharmacokinetic interactions between donafenib and empagliflozin or henagliflozin , lenvatinib and empagliflozin or henagliflozin in rats
  • Preprint
  • File available

June 2024

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39 Reads

Donafenib(DONA) and lenvatinib(LEN) are small-molecule tyrosine kinase inhibitors(TKI) that are used to treat advanced hepatocellular carcinoma(HCC).Empagliflozin and henagliflozin are sodium-glucose cotransporter 2(T2DM) inhibitors that are used to treat type 2 diabetes(T2DM).Empagliflozin and henaglifiozin are uridine diphosphate glucuronosyltransferase(UGT)1A9, Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)Donafenib is metabolized by UGT1A9 and is an inhibitor of UGT1A9 and lenvatinib is a substrate for P-gp and BCRP.T2DM is one of the risk factors for HCC progression, so the two drugs may be used in combination in clinical practice, but there is a lack of clear information about drug interactions. Therefore, the present study aimed to reveal the extent of drug interactions between donafenib, lenvatinib and empagliflozin and henagliflozin in rats and explore the possible mechanisms.Rats were divided into fourteen groups (n = 6) that received empaglifiozin(1,2),henagliflozin(3,4,)donafenib(5), lenvatinib(6), empaglifiozin and donafenib (7), hennagliflozin and donafenib (8), empaglifiozin and lenvatinib(9) ,henagliflozin and lenvatinib (10),donafenib and empaglifiozin (11), donafenib and henagliflozin (12),lenvatinib and empaglifiozin(13),lenvatinib and henagliflozin(14). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA) expressions were measured by quantitative RT-PCR. Multiple administration of empagliflozin reduced the area under the concentration-time curve (AUC0 − t and AUC0−∞) of donafenib by 33.46% and 32.7% respectively. The apparent clearance rate (CLz/F) and apparent volume of distribution (Vd/F) were reduced by 66.7% and 95.2%, respectively. The half-life (T1/2) was prolonged by 17.6%.Henagliflozin modest decreased donafenib AUC0 − t and AUC0−∞ by 27.8% and 26.9%. The CLz/F of donafenib was 2.6-fold compared to the control group.Multiple doses of donafenib caused empagliflozin to AUC0 − t and AUC0−∞ increased by 57.5%and58.5%. CLz/F were significantly decreased by 39.9% .The combination of multiple doses of donafenib increased the maximum plasma concentration (Cmax) of henagliflozin by 65.5%, AUC0 − t and AUC0−∞ by 177.0% and178.0%, respectively. CLz/F and Vz/F of hanagliflozin were decreased by 64.1% and 45.1%.Multiple administration of empagliflozin decreased the AUC0 − t and AUC0−∞ of lenvatinib by 18.7% and21.4%, respectively. CLz/F was accelerated by 30.0%. After multiple administration of constant gliflozin, the AUC0 − t and AUC0−∞ of lenvatinib decreased by 20.3% and 20.9%, respectively, and CLz/F increased by 1.30-flod.Multiple doses of lenvatinib had no significant effect on the pharmacokinetics of empagliflozin and henagliflozin.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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In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

October 2023

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61 Reads

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2 Citations

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.


Efficacy and influencing factor analysis of Voriconazole in the treatment of invasive fungal infections

August 2023

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8 Reads

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1 Citation

Diagnostic Microbiology and Infectious Disease

Current study aims to explore the correlation between the administered dose and efficacy of voriconazole in the treatment of invasive fungal infection (IFI). The correlation between different doses of Voriconazole and plasma concentrations as well as clinical efficacy was counted. Consequently, 40 strains of pathogenic micro-organisms were isoninelated and cultured from etiological samples. A total of 66 patients with steady-state trough serum concentrations ranging from 1.0 to 5.5 μg/mL were measured, with a compliance rate of 79.5%. Chi-square test showed that there was a significant correlation between Voriconazole steady-state serum trough concentration and treatment efficacy. In addition, the result of Pearson test showed that steady-state trough serum concentration of Voriconazole was significantly positively correlated with the administered dose (γ = 0.866, P < 0.001). On conclusion, Voriconazole is effective in treatment of IFI, and there is a significant dose-plasma concentration correlation with efficacy.


In vivo assessment of the pharmacokinetic interactions between donafenib and dapagliflozin, donafenib and canagliflozin in rats

April 2023

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6 Reads

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4 Citations

Biomedicine & Pharmacotherapy

Donafenib (DONA), a deuterium derivative of sorafenib, is used for advanced hepatocellular carcinoma (HCC). Dapagliflozin (DAPA) and canagliflozin (CANA) are sodium-glucose co-transporter 2 (SGLT2) inhibitors used for T2DM, which is frequently comorbid with HCC. Three drugs are substrates of UGT1A9 isoenzyme. This study aimed to evaluate donafenib-dapagliflozin and donafenib-canagliflozin pharmacokinetic interactions and explore the potential mechanisms. Rats were divided into seven groups (n = 6) that received donafenib (1), dapagliflozin (2), canagliflozin (3), dapagliflozin and donafenib (4), canagliflozin and donafenib (5), donafenib and dapagliflozin (6), donafenib and canagliflozin (7). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA) expressions were measured by quantitative RT-PCR. Multiple doses of dapagliflozin caused donafenib maximum plasma concentration (Cmax) to increase 37.01%. Canagliflozin increased donafenib Cmax 1.77-fold and the area under the plasma concentration-time curves (AUC0-t and AUCinf) 1.39- and 1.41-fold, respectively, while reducing the apparent clearance (CLz) 28.38%. Multiple doses of donafenib increased dapagliflozin AUC0-t 1.61-fold, AUCinf 1.77-fold, whereas its CLz reduced 40.50%. Furthermore, donafenib caused similar changes in canagliflozin pharmacokinetics. The PCR results demonstrated that dapagliflozin inhibited the mRNA expression of Ugt1a7 in liver and donafenib decreased the expression of Ugt1a7 mRNA in liver and intestine. Increased exposure to these drugs may be due to their metabolism inhibition mediated by Ugt1a7. These pharmacokinetic interactions observed in this study may be of clinical significance, which may help adjust dose properly and avoid toxicity effects in patients with HCC and T2DM.


Figure 7. MS/MS spectra of all metabolites of galangin in vitro and in vivo. Figure 7. MS/MS spectra of all metabolites of galangin in vitro and in vivo.
Establishment of quality loss template.
Summary of phase I and phase II metabolites of galangin in rat liver microsomes, intestinal bacteria, blood, urine, bile, feces, and tissue samples.
Cont.
Analysis of Galangin and Its In Vitro/In Vivo Metabolites via Ultra-High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

October 2022

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48 Reads

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7 Citations

Metabolites

Galangin, a naturally available flavonoid, induces a variety of pharmacological activities and biological effects via several mechanisms. However, in vivo metabolism of galangin has not been fully explored, which means knowledge of its pharmacodynamics and application potential is limited. The objective of this study was to establish an ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry method for the rapid profiling and identification of galangin metabolites in vitro and in vivo using unique online information-dependent acquisition with multiple mass defect filtering combined with dynamic background subtraction in positive ion mode. A total of 27 metabolites were detected and characterized, among which eight metabolites in liver microsomes and four metabolites in intestinal microflora were characterized, and 27 metabolites from rat plasma, bile, urine, feces, and a number of different tissue samples were characterized. Thirteen major metabolic pathways including hydrogenation, hydroxylation, glycosylation, methylation, acetylation, glucuronidation, and sulfation were observed to be attributable to the biotransformation of the metabolites. This study provides evidence for the presence of in vitro and in vivo metabolites and the pharmacokinetic mechanism of galangin. Moreover, the study promotes the further development and utilization of galangin and the plant from which it is derived, Alpinia officinarum Hance.


Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC-MS/MS

October 2022

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4 Reads

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4 Citations

Biomedical Chromatography

Almonertinib was included in the first-line treatment of non-small cell lung cancer (NSCLC) with EGFR T790M mutations by the Chinese Society of Clinical Oncology (CSCO) in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid-liquid extraction with tert-butyl methyl ether, an XSelect HSS T3 column (2.1×100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib-D3 (internal standard, IS). The analytes were detected using an AB Sciex Triple Quad 5500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5-200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results.


Development of UPLC-MS/MS Method to Study the Pharmacokinetic Interaction between Sorafenib and Dapagliflozin in Rats

September 2022

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50 Reads

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7 Citations

Molecules

Sorafenib (SOR), an inhibitor of multiple kinases, is a classic targeted drug for advanced hepatocellular carcinoma (HCC) which often coexists with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a sodium–glucose cotransporter-2 inhibitor (SGLT2i), is widely used in patients with T2DM. Notably, co-administration of SOR with DAPA is common in clinical settings. Uridine diphosphate-glucuronosyltransferase family 1 member A9 (UGT1A9) is involved in the metabolism of SOR and dapagliflozin (DAPA), and SOR is the inhibitor of UGT1A1 and UGT1A9 (in vitro). Therefore, changes in UGT1A9 activity caused by SOR may lead to pharmacokinetic interactions between the two drugs. The objective of the current study was to develop an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of SOR and DAPA in plasma and to evaluate the effect of the co-administration of SOR and DAPA on their individual pharmacokinetic properties and the mechanism involved. The rats were divided into four groups: SOR (100 mg/kg) alone and co-administered with DAPA (1 mg/kg) for seven days, and DAPA (1 mg/kg) alone and co-administered with SOR (100 mg/kg) for seven days. Liquid–liquid extraction (LLE) was performed for plasma sample preparation, and the chromatographic separation was conducted on Waters XSelect HSS T3 column with a gradient elution of 0.1% formic acid and 5 mM ammonium acetate (Phase A) and acetonitrile (Phase B). The levels of Ugt1a7 messenger RNA (mRNA) were determined in rat liver and intestine using quantitative real-time polymerase chain reaction (qRT-PCR). The method was successfully applied to the study of pharmacokinetic interactions. DAPA caused a significant decrease in the maximum plasma concentrations (Cmax) and the area under the plasma concentration–time curves (AUC0–t) of SOR by 41.6% and 50.5%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) significantly increased 2.85- and 1.98-fold, respectively. When co-administering DAPA with SOR, the AUC0–t and the elimination half-life (t1/2Z) of DAPA significantly increased 1.66- and 1.80-fold, respectively, whereas the CLz/F significantly decreased by 40%. Results from qRT-PCR showed that, compared with control, seven days of SOR pretreatment decreased Ugt1a7 expression in both liver and intestine tissue. In contrast, seven days of DAPA pretreatment decreased Ugt1a7 expression only in liver tissue. Therefore, pharmacokinetic interactions exist between long-term use of SOR with DAPA, and UGT1A9 may be the targets mediating the interaction. Active surveillance for the treatment outcomes and adverse reactions are required.


Figure 1. The structure of sorafenib, lenvatinib, and canagliflozin.
Figure 2. Representative chromatograms of the sorafenib (Ⅰ), lenvatinib (Ⅱ), and canagliflozin (Ⅲ) in rat plasma samples. (A) Rat blank plasma samples; (B) rat blank plasma samples spiked with analytes at the lower limit of quantification level; (C) rat plasma samples after oral administration of analytes; and (D) internal standards in the lower limit of quantification samples.
Pharmacokinetic parameters of sorafenib in rat plasma after oral administration of single dose sorafenib (100 mg/kg) and combined with canagliflozin (10 mg/kg); n = 6 for each group.
Pharmacokinetic parameters of canagliflozin in rat plasma after oral administration of sin- gle dose canagliflozin (10 mg/kg) and combined with sorafenib (100 mg/kg) and lenvatinib (1.2 mg/kg); n = 6 for each group.
Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats

August 2022

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65 Reads

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6 Citations

Molecules

Hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM) are common clinical conditions, and T2DM is an independent risk factor for HCC. Sorafenib and lenvatinib, two multi-targeted tyrosine kinase inhibitors, are first-line therapies for advanced HCC, while canagliflozin, a sodium-glucose co-transporter 2 inhibitor, is widely used in the treatment of T2DM. Here, we developed an ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of canagliflozin, sorafenib, and lenvatinib, and investigated the pharmacokinetic drug interactions between canagliflozin and sorafenib or lenvatinib in rats. The animals were randomly divided into five groups. Groups І–Ш were gavage administrated with sorafenib, lenvatinib, and canagliflozin, respectively. Group Ⅳ received sorafenib and canagliflozin; while group Ⅴ received lenvatinib and canagliflozin. The area under the plasma concentration-time curves (AUC) and maximum plasma concentrations (Cmax) of canagliflozin increased by 37.6% and 32.8%, respectively, while the apparent volume of distribution (Vz/F) and apparent clearance (CLz/F) of canagliflozin significantly decreased (30.6% and 28.6%, respectively) in the presence of sorafenib. Canagliflozin caused a significant increase in AUC and Cmax of lenvatinib by 28.9% and 36.2%, respectively, and a significant decrease in Vz/F and CLz/F of lenvatinib by 52.9% and 22.7%, respectively. In conclusion, drug interactions exist between canagliflozin and sorafenib or lenvatinib, and these findings provide a reference for the use of these drugs in patients with HCC and T2DM.


Figure 3. The chromatogram of analytes and IS in blank plasma (I). The chromatogram of ana and IS at LLOQ concentration levels (II); (A) osimertinib; (B) aumolertinib; (C) furmonertinib IS.
Precision and accuracy data of osimertinib, aumolertinib, and furmonertinib in human plasma (n = 6).
Stability of analytes in human plasma under various storage conditions (mean ± SD, n = 6, %).
Cont.
Steady-state trough concentrations of analytes in patient plasma.
Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

July 2022

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117 Reads

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10 Citations

Molecules

The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib, aumolertinib, and furmonertinib represent a new treatment option for patients with EGFR p.Thr790 Met (T790 M)-mutated non-small cell lung cancer (NSCLC). Currently, there are no studies reporting the simultaneous quantification of these three drugs. A simple ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of osimertinib, aumolertinib, and furmonertinib concentrations in human plasma, and it was applied for therapeutic drug monitoring (TDM). Plasma samples were processed using the protein precipitation method (acetonitrile). A positive ion monitoring mode was used for detecting analytes. D3-Sorafenib was utilized as the internal standard (IS), and the mobile phases were acetonitrile (containing 0.1% formic acid) and water with gradient elution on an XSelect HSS XP column (2.1 mm × 100.0 mm, 2.5 µm, Waters, Milford, MA, USA) at a flow rate of 0.5 mL·min−1. The method’s selectivity, precision (coefficient of variation of intra-day and inter-day ≤ 6.1%), accuracy (95.8–105.2%), matrix effect (92.3–106.0%), extraction recovery, and stability results were acceptable according to the guidelines. The linear ranges were 5–500 ng·mL−1, 2–500 ng·mL−1, and 0.5–200 ng·mL−1 for osimertinib, aumolertinib, and furmonertinib, respectively. The results show that the method was sensitive, reliable, and simple and that it could be successfully applied to simultaneously determine the osimertinib, aumolertinib, and furmonertinib blood concentrations in patients. These findings support using the method for TDM, potentially reducing the incidence of dosing blindness and adverse effects due to empirical dosing and inter-patient differences.


Citations (25)


... Following the exclusion of 1,154 duplicates, 2,138 studies underwent title and abstract screening. Ultimately, 60 studies were selected for qualitative synthesis based on a full-text review (Aiuchi et al., 2022;Allegra et al., 2018;Bartelink et al., 2013;Benedict et al., 2023;Blanco-Dorado et al., 2019;Boast et al., 2016;Cabral-Galeano et al., 2015;Chaudhri et al., 2020;Chen C. Y. et al., 2022;Cheng et al., 2020;Choi et al., 2013;Chuwongwattana et al., 2016;Cojutti et al., 2016;Dolton et al., 2012;Dorado et al., 2020;Dote et al., 2016;Duehlmeyer et al., 2021;Ebrahimpour et al., 2017;Fan et al., 2022;Hashemizadeh et al., 2017;Hoenigl et al., 2013;Hu et al., 2018;Hu et al., 2023;Huang et al., 2023;Huang et al., 2020;Jia et al., 2021;Kang et al., 2015;Kim et al., 2014;Lempers et al., 2019;Li et al., 2020;Li et al., 2023;Liu et al., 2017;Mafuru et al., 2021;Miao et al., 2019;Myrianthefs et al., 2010;Pieper et al., 2012;Ronda et al., 2023;Ruiz et al., 2019;Saini et al., 2014;Shao et al., 2017;Shen et al., 2022;Soler-Palacin et al., 2012;Takahashi et al., 2020;Tian et al., 2021;Troke et al., 2011;Valle-T-Figueras et al., 2021;Wei et al., 2019;Yan et al., 2018;Yang et al., 2023;Ye et al., 2022;Yi et al., 2017;Zeng et al., 2020;Zhang et al., 2023;Zhao et al., 2021a;Zhao et al., 2021b;Zhao Y. C. et al., 2021;Zhou et al., 2020). Of the 60 articles, 58 studies were included in the quantitative synthesis. ...

Reference:

Associated factors with voriconazole plasma concentration: a systematic review and meta-analysis
Efficacy and influencing factor analysis of Voriconazole in the treatment of invasive fungal infections
  • Citing Article
  • August 2023

Diagnostic Microbiology and Infectious Disease

... The former and the latter are obtained by a successive loss of CO 2 and CO groups. The middle fragment appeared after the detachment of two CO moieties from the molecular ion [71]. In the case of kaempferide (C 16 H 12 O 6 ), eluted in the 22.9 min as an m/z of 299.0561, the loss of a hydroxyl group was observed (m/z of 284.0318) together with the Diels-Alder reaction of flavonoid ring fragmentation (m/z of 151.0029) [71]. ...

Analysis of Galangin and Its In Vitro/In Vivo Metabolites via Ultra-High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

Metabolites

... In studies of metabolic stability, pharmacokinetics, DDI and TDM of different analytes in different matrices, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/ MS) has become the reference tool because of its high selectivity and efficiency of quantification Attwa, AlRabiah, et al. 2023;). Reports of UPLC-MS/MS assays to investigate almonertinib have been published, while the determination of HAS-719 (the main metabolite of almonertinib) was not mentioned and the long run time (>3 min) was not suitable for analyzing large numbers of samples in these studies Fu et al. 2023;Tang et al. 2022). However, only one methodological study involved the simultaneous detection of almonertinib and HAS-719, but this assay used isotope-labeled internal standard (IS), which was expensive and not commercially available in the common laboratory (Liu et al. 2022). ...

Effects of voriconazole and fluconazole on the pharmacokinetics of almonertinib in rats by UPLC-MS/MS
  • Citing Article
  • October 2022

Biomedical Chromatography

... Currently, there are scarce reported methods for the determination of DAP in biological fluids [7]. However, a recently developed method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) can accurately determine DAP in normal Sprague-Dawley rats as well as in diabetic rats, in support of preclinical studies [8]. In the negative electrospray ionization mode, an LC-MS/MS assay was described for selected reaction monitoring (SRM) detection of DAP-acetate adduct ions in human plasma [9]. ...

Development of UPLC-MS/MS Method to Study the Pharmacokinetic Interaction between Sorafenib and Dapagliflozin in Rats

Molecules

... The aim of this study was to evaluate the pharmacokinetics of dor nide versus empagli ozin,donafenib versus henagli ozin, lenvatinib versus empagli ozin, and lenvatinib versus hengagli ozin using ultra-high performance liquid chromatography -tandem mass spectrometry (UPLC-MS/MS). Our research group has established a method for the determination of lenvatinib [41] and donafenib [25] , so this experiment establ-ished a method for the simultaneous determination of empagli ozin and hengagli ozin. These results may help to determine the potential pharmacokinetics of co-agents in cancer patients, contributing to clinical practice. ...

Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats

Molecules

... These steady-state concentrations were within the ranges previously reported for 80-mg dosing in patients with NSCLC. [41][42][43][44][45] The Bland-Altman mean difference plot had high concordance between plasma and finger-prick DBS measurements (Fig. 4). For osimertinib, AZ5104, and AZ7550, a mean concentration difference of 0.4%, 23.5%, and 23.4% between plasma and hemaPEN DBS was observed, respectively, indicating no significant difference for measuring osimertinib with a minor plasma bias for both metabolite concentrations. ...

Determination of Osimertinib, Aumolertinib, and Furmonertinib in Human Plasma for Therapeutic Drug Monitoring by UPLC-MS/MS

Molecules

... This issue has also been observed for TKIs other than those used for advanced HCC [59]. A possible solution to enhance oral bioavailability is the co-administration with substances apparently able to increase absorption of the single drugs [60,61]; alternative formulations designed for parenteral use could also overcome this problem. Indeed, a sorafenib microcrystalline formulation for intratumoral injection demonstrated a possible long-acting effect associated with less adverse events than the oral formulation [58], as well as a regorafenib nanodrug preparation studied for intravenous administration showed a significant increase of plasma concentration and therapeutic efficacy on murine models [34]. ...

Influence of schisantherin A on the pharmacokinetics of lenvatinib in rats and its potential mechanism
  • Citing Article
  • January 2021

Journal of Gastrointestinal Oncology

... The concurrent administration of lenvatinib with telmisartan (rho = −0.10) resulted in reduced systemic exposure to telmisartan, indicating potential pharmacokinetic interactions between these two drugs [50]. These reported findings substantiate the reliability of our data and warrant further investigation into the potential drug combinations we have identified (Figure 4c). ...

A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

Molecules

... Radix Astragali (Huangqi) is a commonly used traditional Chinese medicine in cardiovascular treatments, often prescribed in herbal or patent medicine formulations [10][11][12]. Among its numerous ingredients, astragaloside IV (ASIV) is the main active component used to treat HF. ...

QiShenYiQi pills, a Chinese patent medicine, increase bioavailability of atorvastatin by inhibiting Mrp2 expression in rats

... Therefore, further research is needed to better understand the pharmacological properties of lenvatinib. Knowing the fate of the drug in rats may be relevant and helpful as rats tend to be a suitable model organism (17)(18)(19)(20). ...

UPLC-MS/MS method for the determination of Lenvatinib in rat plasma and its application to drug-drug interaction studies
  • Citing Article
  • November 2021

Journal of Pharmaceutical and Biomedical Analysis