Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma

Morival, Camille; Oumari, Sitty; Lenglet, Arthur; Corre, Pascal Le

doi:10.1002/hon.2485

Cited by 5 publications

(3 citation statements)

References 71 publications

(96 reference statements)

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“…The obtained data indicate low solubility and low lipophilicity, which is independent of pH. Our data seems to underline the inclusion of POM as a BCS class IV drug [ 3 , 26 ]and justified the application of CD complexation to increase POM solubility.…”

Section: Resultssupporting

confidence: 67%

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Szabó

Orban

Borbás

et al. 2021

Heliyon

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Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins – differing in cavity size, nature of substituents, degree of substitution and charge – the highest solubility increase was observed with sulfobutylether-β-cyclodextrin (SBE-β-CD). The inclusion complexation between POM and SBE-β-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the A L -type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-β-CD could be a promising approach for developing more effective POM formulations with increased solubility.

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Section: Resultssupporting

confidence: 67%

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Szabó

Orban

Borbás

et al. 2021

Heliyon

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“…Extensive metabolizers may be at a high risk of side effects. As a result, the CYP2C19 genotype and the CYP2C19 inhibitors or inducers could influence exposure to the active metabolite of THD [161]. Furthermore, adverse effects of THD on the central nervous system CNS, including dizziness, sleepiness, and focusing problems, may be exacerbated by alcohol intake while using THD.…”

Section: Thalidomide Drug Interactionsmentioning

confidence: 99%

Potential Use of Thalidomide in Glioblastoma Treatment: An Updated Brief Overview

Eatmann

Hamouda

et al. 2023

Metabolites

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Glioblastoma is the most common malignant primary brain tumor in adults. Thalidomide is a vascular endothelial growth factor inhibitor that demonstrates antiangiogenic activity, and may provide additive or synergistic anti-tumor effects when co-administered with other antiangiogenic medications. This study is a comprehensive review that highlights the potential benefits of using thalidomide, in combination with other medications, to treat glioblastoma and its associated inflammatory conditions. Additionally, the review examines the mechanism of action of thalidomide in different types of tumors, which may be beneficial in treating glioblastoma. To our knowledge, a similar study has not been conducted. We found that thalidomide, when used in combination with other medications, has been shown to produce better outcomes in several conditions or symptoms, such as myelodysplastic syndromes, multiple myeloma, Crohn’s disease, colorectal cancer, renal failure carcinoma, breast cancer, glioblastoma, and hepatocellular carcinoma. However, challenges may persist for newly diagnosed or previously treated patients, with moderate side effects being reported, particularly with the various mechanisms of action observed for thalidomide. Therefore, thalidomide, used alone, may not receive significant attention for use in treating glioblastoma in the future. Conducting further research by replicating current studies that show improved outcomes when thalidomide is combined with other medications, using larger sample sizes, different demographic groups and ethnicities, and implementing enhanced therapeutic protocol management, may benefit these patients. A meta-analysis of the combinations of thalidomide with other medications in treating glioblastoma is also needed to investigate its potential benefits further.

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“…Pharmacokinetic drug interactions involving inhibitors and inducers of P450 CYP3A4 can result in either increases or decreases in serum concentrations of drugs, potentially leading to enhanced toxicity or treatment failure [1,2]. However, drug-drug interactions involving membrane transporters should also be considered [3,4]. Pharmacodynamic drug interactions in HSCT patients are also likely but are less studied [5].…”

Section: Introductionmentioning

confidence: 99%

Potential drug–drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay

Sánchez

Bacle

Lamy

et al. 2019

Cancer Chemother Pharmacol

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Purpose: Studies have documented potential drug-drug interactions (pDDI's) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents and supportivecare drugs, studies on potential DDI's are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDI's, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay. Method: retrospective study in 31 adult patients consecutively admitted to the BMTU. Results: Prevalence of pharmacokinetic interactions was 10-time lower than the pharmacodynamic interactions. The contra-indications were rare, and only of pharmacokinetic origin. The main drugs involved in pharmacokinetic DDI's were ciclosporine, methotrexate, esomeprazole, tramadol and vincristine. The median number of potential nephrotoxicity-related DDI's per patient was 7 and the median number of days during which nephrotoxicity-related DDI's potentially occurred was 77 days per patient. The decrease in glomerular filtration rate (GFR) throughout the BMTU stay (mean decrease of 13 ml/min) was correlated with the number of days of potential nephrotoxic drug interactions. Conclusions: Potential DDI's in HCST patients in BMTU were quite common. The DDI's from pharmacokinetic origin were less frequent, but of higher grade, than those of pharmacodynamic origin. The decrease in GFR suggests that the density of potential nephrotoxic drug interactions may be an issue to be considered in these patients.

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Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma

Cited by 5 publications

References 71 publications

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Potential Use of Thalidomide in Glioblastoma Treatment: An Updated Brief Overview

Potential drug–drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay

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