Variability in bioavailability of small molecular tyrosine kinase inhibitors

Herbrink, Maikel; Nuijen, Bastiaan; Schellens, Jan H.M.; Beijnen, Jos H.

doi:10.1016/j.ctrv.2015.03.005

Cited by 111 publications

(116 citation statements)

References 184 publications

(164 reference statements)

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“…The hosting of LAP within HSA deserves specific comment. Tyrosine kinase inhibitors are notoriously insoluble in water, which is one of the reasons why this class of drug has poor oral bioavailability (47). Additionally, although clinical trials have demonstrated that the combination of LAP with other HER2 directed therapies for dual blockade is of benefit in certain subgroups of patients (48), severe toxicities, diarrhea in particular, are leading to poor compliance and treatment discontinuation (49).…”

Section: Resultsmentioning

confidence: 99%

Near-infrared remotely triggered drug-release strategies for cancer treatment

Goodman

Neumann

Nørregaard

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO 2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects. chemotherapy | cancer | drug release | near-infrared | nanoparticle

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Section: Resultsmentioning

confidence: 99%

Near-infrared remotely triggered drug-release strategies for cancer treatment

Goodman

Neumann

Nørregaard

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…For several TKIs approved by the FDA, the effect on bioavailability has only been studied in vitro, whereas pH-dependent solubility and TKI absorption in vivo is often multifactorial [4]. In this case, only preclinical in vitro data on chemical pH-dependent solubility may not predict the true in vivo effects on bioavailability (e.g.…”

Section: Unraveling Drug–drug Interactions Between Tyrosine Kinase Inmentioning

confidence: 99%

“…Use of the oral administration route of TKIs offers logistic flexibility and is convenient for the patient [3]; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. For TKIs in particular, the poor and variable bioavailability, together with other variable pharmacokinetic factors, contribute to a significant in- and between-patient variability in plasma levels and exposure [4]. Most importantly, acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may decrease the solubility and thereby the biological availability of certain TKIs.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options

et al. 2017

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Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given.

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“…They are all classified as Class IV drugs by BCS and possess similar properties to SUT (Wu et al, 2014, Herbrink et al, 2015.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

et al. 2017

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Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib-polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple L-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa5Mw5 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC 50 value against MCF-7 cells.

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Variability in bioavailability of small molecular tyrosine kinase inhibitors

Cited by 111 publications

References 184 publications

Near-infrared remotely triggered drug-release strategies for cancer treatment

Near-infrared remotely triggered drug-release strategies for cancer treatment

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

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