Monitoring imatinib plasma concentrations in chronic myeloid leukemia

Martins, Darlize Hübner; Wagner, Sandrine Comparsi; Santos, Tamyris Vianna dos; Lizot, Lilian de Lima Feltraco; Antunes, Marina Venzon; Capra, Marcelo; Linden, Rafael

doi:10.5581/1516-8484.20110081

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…HPLC coupled to MS (HPLC-MS) has become the reference method for the quantification of large volumes of drugs in biological fluids (20). The coupling of these two techniques combines the advantages of chromatography (high separation selectivity and efficiency) with the advantages of MS (obtaining information on the structure, increase in mass and selectivity) (67). Consequently, the combination of TKIs has been used as a strategy to prevent the development of resistance against these molecules.…”

Section: Practical Issues In Tdm: Application For Routine Analysismentioning

confidence: 99%

Therapeutic drug monitoring and tyrosine kinase inhibitors

et al. 2016

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Abstract. The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under-or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects. Following a literature search on PubMed, studies on TKIs and their pharmacokinetic characteristics, plasma quantification and inter-individual variability was studied. TDM is commonly used in various medical fields, including cardiology and psychiatry, but is not often applied in oncology. Plasma concentration monitoring has been thoroughly studied for imatinib, in order to evaluate the usefulness of TDM. The measurement of plasma concentration can be performed by various analytical techniques, with liquid chromatography-mass spectrometry being the reference method. This method is currently used to monitor the efficacy and tolerability of imatinib treatments. Although TDM is already being used for imatinib, additional studies are required in order to improve this practice with the inclusion of other TKIs.

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Section: Practical Issues In Tdm: Application For Routine Analysismentioning

confidence: 99%

Therapeutic drug monitoring and tyrosine kinase inhibitors

et al. 2016

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“…According to clinical data, IM is well‐tolerated and can be given orally with bioavailability of 98%, in the treatment of CML (Martins et al, ). This treatment with IM achieves a complete haematological remission rate of above 95% and a major cytogenetic response rate above 80% (Singh et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…This treatment with IM achieves a complete haematological remission rate of above 95% and a major cytogenetic response rate above 80% (Singh et al, ). The standard dose of IM is 400 mg·day −1 for patients with chronic‐phase CML and 600 mg·day −1 for accelerated phase or blast crisis of CML (Martins et al, ). The efficacy of the threshold plasma trough concentration (C 0 ) of IM must be set above 1000 ng·mL −1 (1.7 μM) to achieve optimized activity (Martins et al, ).…”

Section: Discussionmentioning

confidence: 99%

Suppression of carboxylesterases by imatinib mediated by the down‐regulation of pregnane X receptor

Luo

Xia

et al. 2017

British J Pharmacology

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“…43 As with dasatinib, myelosuppression is the most common AE and usually occurs during the first few months of treatment. 43 As with dasatinib, myelosuppression is the most common AE and usually occurs during the first few months of treatment.…”

Section: Adverse Effectsmentioning

confidence: 99%

“…229 An increase in dose beyond 1500 mg once weekly or twice weekly when used in treating solid malignancies did not increase plasma gefitinib concentrations in a linear fashion. 1,43 In GIST, greatest clinical benefit was observed at predose concentrations of 1.1 mg/L or more. 211 The rate of complete cytogenetic response in CML seems to be related to imatinib plasma concentration with a suggested target for predose plasma imatinib of 1 mg/L or more.…”

Section: Gefitinibmentioning

confidence: 99%

Clinical Pharmacokinetics of Tyrosine Kinase Inhibitors

Josephs

Fisher

Spicer

et al. 2013

Therapeutic Drug Monitoring

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The treatment of many malignancies has been improved in recent years by the introduction of molecular targeted therapies. These drugs interact preferentially with specific targets that are mutated and/or overexpressed in malignant cells. A group of such targets are the tyrosine kinases, against which a number of inhibitors (tyrosine kinase inhibitors, TKIs) have been developed. Imatinib, a TKI with targets that include the breakpoint cluster region-Abelson (bcr-abl) fusion protein kinase and mast/stem cell growth factor receptor kinase (c-Kit), was the first clinically successful drug of this type and revolutionized the treatment and prognosis of chronic myeloid leukemia and gastrointestinal stromal tumors. This success paved the way for the development of other TKIs for the treatment of a range of hematological malignancies and solid tumors. To date, 14 TKIs have been approved for clinical use and many more are under investigation. All these agents are given orally and are substrates of a range of drug transporters and metabolizing enzymes. In addition, some TKIs are capable of inhibiting their own transporters and metabolizing enzymes, making their disposition and metabolism at steady-state unpredictable. A given dose can therefore give rise to markedly different plasma concentrations in different patients, favoring the selection of resistant clones in the case of subtherapeutic exposure, and increasing the risk of toxicity if dosage is excessive. The aim of this review was to summarize current knowledge of the clinical pharmacokinetics and known adverse effects of the TKIs that are available for clinical use and to provide practical guidance on the implications of these data in patient management, in particular with respect to therapeutic drug monitoring.

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Monitoring imatinib plasma concentrations in chronic myeloid leukemia

Cited by 16 publications

References 33 publications

Therapeutic drug monitoring and tyrosine kinase inhibitors

Therapeutic drug monitoring and tyrosine kinase inhibitors

Suppression of carboxylesterases by imatinib mediated by the down‐regulation of pregnane X receptor

Clinical Pharmacokinetics of Tyrosine Kinase Inhibitors

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