Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy

2016 ◽  
Vol 35 (3) ◽  
pp. 259-280 ◽  
Author(s):  
Caroline Gay ◽  
Delphine Toulet ◽  
Pascal Le Corre
Keyword(s):  
Cytochrome P450 ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Acid Suppression ◽  
Acid Suppression Therapy ◽  
Pharmacokinetic Drug

scholarly journals Pharmacokinetics of Dasatinib

2019 ◽  
Vol 120 (2-3) ◽  
pp. 52-63 ◽  
Author(s):  
Jana Hořínková ◽  
Martin Šíma ◽  
Ondřej Slanař
Keyword(s):  
Cytochrome P450 ◽  
Chronic Myeloid Leukaemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukaemia ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Gastric Ph ◽  
Simultaneous Administration ◽  
Essential Tool ◽  
Pharmacokinetic Properties

Tyrosine kinase inhibitors have recently become an essential tool in management of chronic myeloid leukaemia (CML). Dasatinib, a representative of those drugs, acts by inhibiting key proteins included in CML development, predominantly Bcr-Abl and Src. Its advantage is that it shows activity in many cases where other agents bring no improvement due to resistance. Pharmacokinetics of dasatinib has specific characteristics that may play an important role in achieving sufficient exposure in patients. Therefore, the key pharmacokinetic properties are summarized in this report. For example, dasatinib absorption is significantly influenced by gastric pH and its modulation can be a source of serious interactions, as well as simultaneous administration of drugs affecting cytochrome P450.

scholarly journals Drug interactions between tyrosine-kinase inhibitors and acid suppressive agents: more than meets the eye–Authors' reply

2014 ◽  
Vol 15 (11) ◽  
pp. e470-e471 ◽  
Author(s):  
Roelof W F van Leeuwen ◽  
Teun van Gelder ◽  
Ron H J Mathijssen ◽  
Frank G A Jansman
Keyword(s):  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors

scholarly journals Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids

2015 ◽  
Vol 3 (4) ◽  
pp. 245-260 ◽  
Author(s):  
Christa P. Bénit ◽  
Charles J. Vecht
Keyword(s):  
Drug Metabolism ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Large Individual ◽  
Pharmacokinetic Studies ◽  
Chemotherapeutic Drugs

Abstract Patients with cancer commonly experience seizures. Combined therapy with anticonvulsant drugs (AEDs) and chemotherapeutic drugs or tyrosine kinase inhibitors carries inherent risks on drug-drug interactions (DDIs). In this review, pharmacokinetic studies of AEDs with chemotherapeutic drugs, tyrosine kinase inhibitors, and glucocorticoids are discussed, including data on maximum tolerated dose, drug clearance, elimination half-life, and organ exposure. Enzyme-inducing AEDs (EIAEDs) cause about a 2-fold to 3-fold faster clearance of concurrent chemotherapeutic drugs metabolized along the same pathway, including cyclophosphamide, irinotecan, paclitaxel, and teniposide, and up to 4-fold faster clearance with the tyrosine kinase inhibitors crizotinib, dasatinib, imatinib, and lapatinib. The use of tyrosine kinase inhibitors, particularly imatinib and crizotinib, may lead to enzyme inhibition of concurrent therapy. Many of the newer generation AEDs do not induce or inhibit drug metabolism, but they can alter enzyme activity by other drugs including AEDs, chemotherapeutics and tyrosine kinase inhibitors. Glucocorticoids can both induce and undergo metabolic change. Quantitative data on changes in drug metabolism help to apply the appropriate dose regimens. Because the large individual variability in metabolic activity increases the risks for undertreatment and/or toxicity, we advocate routine plasma drug monitoring. There are insufficient data available on the effects of tyrosine kinase inhibitors on AED metabolism.

Drug interactions between tyrosine-kinase inhibitors and acid suppressive agents: more than meets the eye

2014 ◽  
Vol 15 (11) ◽  
pp. e469-e470 ◽  
Author(s):  
Guo Yu ◽  
Qing-Shan Zheng ◽  
Da-Xin Wang ◽  
Hong-Hao Zhou ◽  
Guo-Fu Li
Keyword(s):  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors

Prevalence of the concurrent administration of contraindicated medications in patients with cancer treated with tyrosine kinase inhibitors (TKIs): A pilot study from the IU Simon Comprehensive Cancer Center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18714-e18714
Author(s):  
Dana Alhaffar ◽  
Yan Han ◽  
Julianne Darling ◽  
Todd C. Skaar ◽  
Christopher A. Fausel ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Concurrent Administration ◽  
Patients With Cancer ◽  
Drug Drug Interaction

e18714 Background: Polypharmacy may result in drug-drug interactions that reduce efficacy or increase toxicities to patients. Tyrosine kinase inhibitors (TKIs), which is standard therapy for many patients with cancer, have interactions with many commonly prescribed drugs (including proton pump inhibitors [PPIs] and cytochrome inhibitors/inducers) which alter their metabolism. Methods: Retrospective study of 100 consecutively chosen patients with advanced cancer treated with TKIs were identified. Patients < 18 years of age, participating in clinical trials, or taking an investigational treatment for their cancer were excluded. TKI start date and concurrent medications were identified from chart reviews. Documentation was undertaken to record co-administration of drugs that could prolong QT interval, PPIs, and CYP3A inhibitors and inducers. QT prolonging medications were divided into those with known risk (KR), conditional risk (CR), and probable risk (PR). IUSM Clinical Pharmacology Flockhart table was utilized for cytochrome drug interactions. All three categories of cytochrome inhibitors (strong, moderate, and weak) were included in the analysis. The primary objective was to estimate the percentage of patients treated with TKIs co-administered these classes of drugs with a potential for harmful drug-drug interaction. Results: Median age of 100 pts was 57 and median duration of treatment with the TKI was 441 days. 85 of 100 pts receiving TKIs for their cancer were also prescribed at least 1 drug with the potential for drug-drug interaction, including 39 with a QT prolonging drug with known risk and 25 with a CYP3A inducer or inhibitor. 53% had documentation of EKG while on TKI treatment. Conclusions: Most patients in this chart review were co-administered TKIs with other agents with a potential for harmful drug-drug interactions. Continual monitoring of medications is necessary to optimize efficacy of TKIs and reduce the chance for harmful side effects.[Table: see text]

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