Pharmacokinetic interaction study of novel combination of palbociclib and sorafenib for hepatocellular carcinoma in SD rats

Paul, David; Chandrakala, Patheparapu; Surendran, Shruti; Prasanth, B.; Satheeshkumar, N.

doi:10.1016/j.jchromb.2019.01.003

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…The t 1/2 was approximately 6.83–14.12 h with a gradual decrease process. The pharmacokinetic properties of SOR in rats in our present findings seem to be consistent with other studies ( Paul et al, 2019 ; Karbownik et al, 2020 ). In addition, what is interesting in these data is that the pharmacokinetic profiles of SOR have been showed marked gender-specific differences.…”

Section: Discussionsupporting

confidence: 94%

“…Wang X et al indicated coadministered with verapamil increased the AUC 0-t and C max of SOR by 58.2 and 57.4%, respectively, in rats mediated by P-gp inhibition ( Wang et al, 2016 ). David Paul revealed that treatment of palbociclib slightly increased the oral bioavailability of SOR in rats by inhibiting the metabolism ( Paul et al, 2019 ). In addition, SoHyun Bae proved that 5, 7-dimethoxyflavone largely enhanced SOR AUC in plasma and most tissues in mice, and the mechanism mediated might be 5,7-DMF significantly increased the effluxion of SOR by inhibiting BCRP by the Bcrp1-dependent manner ( Bae et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption

et al. 2021

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Background: Sorafenib (SOR) is an oral, potent, selective, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used as the first-line therapy for advanced hepatocellular carcinoma (HCC). Baicalin (BG) is used as adjuvant therapy for hepatitis, which accounts for the leading cause of the development of HCC, and is commonly coadministered with SOR in clinic. The purpose of the current study was to characterize the pharmacokinetic changes of SOR and the potential mechanism when SOR is administered concomitantly with BG in rats for single and multiple doses.Methods: Parallel randomized pharmacokinetic studies were performed in rats which received SOR (50 mg/kg, i.g.) alone or coadministered with BG (160 mg/kg, i.g.) for single and multiple doses (7 days). Plasma SOR levels were quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Rat liver microsomes (RLMs) which isolated from their livers were analyzed for CYP3A and SOR metabolism activities. The inhibitory effect of BG on the metabolism of SOR was also assessed in pooled human liver microsomes (HLMs). The effects of BG on the intestine absorption behaviors of SOR were assessed in the in situ single-pass rat intestinal perfusion model.Results: Coadministration with BG (160 mg/kg, i.g.) for single or multiple doses significantly increased the Cmax, AUC0–t, and AUC0–∞ of orally administered SOR by 1.68-, 1.73-, 1.70-fold and 2.02-, 1.65-, 1.66- fold in male rats and by 1.85-, 1.68-, 1.68-fold and 1.57-, 1.25-, 1.24- fold in female rats, respectively (p < 0.01 or p < 0.05). In vitro incubation assays demonstrated that there were no significant differences of Km, Vmax, and CLint of 1-OH MDZ and SOR N-oxide in RLMs between control and multiple doses of BG-treated groups. BG has no obvious inhibitory effects on the metabolism of SOR in HLMs. In comparison with SOR alone, combining with BG significantly increased the permeability coefficient (Peff) and absorption rate constant (Ka) of the SOR in situ single-pass rat intestinal perfusion model.Conclusion: Notably enhanced oral bioavailability of SOR by combination with BG in rats may mainly account for BG-induced SOR absorption. A greater understanding of potential DDIs between BG and SOR in rats makes major contributions to clinical rational multidrug therapy in HCC patients. Clinical trials in humans and HCC patients need to be further confirmed in the subsequent study.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption

et al. 2021

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“…Furthermore, high-cost, limited access stable isotope-labeled internal standards were used, which are hardly affordable for routine clinical laboratories that perform TDM for many different drugs on a daily basis. Other published methods have focused only on one of the drugs of interest, such as PAL [ 20 , 21 ] and RIB [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

et al. 2022

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Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer.

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“…Smith et al introduced the use of an automated micro-sample processing for the pretreatment of mouse plasma samples prior to LC-MS/MS analysis of palbociclib; however, the availability of this system is restricted in many laboratories [9]. Recently, Paul et al described two bioanalytical methods for the quantification of palbociclib in rat plasma using an LC-MS method using a high-resolution quadrupole time of flight (Q-TOF) mass spectrometer, which is more convenient for qualitative rather than quantitative assays; therefore, the instrumentation is restricted in most bioanalytical laboratories [10, 11]. For ribociclib, two bioanalytical assays have been published.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

et al. 2019

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A novel method was developed and validated for the quantification of the three approved CDK4/6 inhibitors (abemaciclib, palbociclib, and ribociclib) in both human and mouse plasma and mouse tissue homogenates (liver, kidney, spleen, brain, and small intestine) using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). For all matrices, pretreatment was performed using 50 μL of sample by protein precipitation with acetonitrile, followed by dilution of the supernatant. Chromatographic separation of the analytes was done on a C18 column using gradient elution. A full validation was performed for human plasma, while a partial validation was executed for mouse plasma and mouse tissue homogenates. The method was linear in the calibration range from 2 to 200 ng/mL, with a correlation coefficient ( r ) ≥0.996 for each analyte. For both human and mouse plasma, the accuracy and precision were within ±15% and ≤15%, respectively, for all concentrations, except for the lower limit of quantification, where they were within ±20% and ≤20%, respectively. A fit-for-purpose strategy was followed for tissue homogenates, and the accuracy and precision were within ±20% and ≤20%, respectively, for all concentrations. Stability of all analytes in all matrices at different processing and storage conditions was tested; ribociclib and palbociclib were unstable in most tissue homogenates and conditions were modified to increase the stability. The method was successfully applied for the analysis of mouse samples from preclinical studies. A new ribociclib metabolite was detected in mouse plasma samples with the same m/z transition as the parent drug. Electronic supplementary material The online version of this article (10.1007/s00216-019-01932-w) contains supplementary material, which is available to authorized users.

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Pharmacokinetic interaction study of novel combination of palbociclib and sorafenib for hepatocellular carcinoma in SD rats

Cited by 12 publications

References 25 publications

Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption

Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment

Development and validation of a bioanalytical method for the quantification of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib in human and mouse matrices using liquid chromatography-tandem mass spectrometry

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