The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

Paris, Justine; Angeli, Eurydice; Bousquet, Guilhem

doi:10.3390/ijms22031281

Cited by 5 publications

(6 citation statements)

References 127 publications

(119 reference statements)

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Section: Future Directionsmentioning

confidence: 99%

“…Intrathecal administration helps drugs to enter the CNS via the lymphatic system 110 . The molecular weight, drugs' biochemical features, and the BBB's efflux systems determine whether drugs can diffuse into deeper brain areas 110 . It has been reported that direct intrathecal injections of trastuzumab can treat meningeal carcinomatosis resulted from breast cancer 111 .…”

Section: Future Directionsmentioning

confidence: 99%

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Breast cancer brain metastasis: Current evidence and future directions

Sun

Dai

et al. 2022

Cancer Medicine

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Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths after lung cancer. Metastasis of the central nervous system is a terrible event for breast cancer patients, affecting their survival and quality of life. Compared with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients, brain metastases are more likely to affect patients with triple-negative breast cancer and human epidermal growth factor receptor 2-positive breast cancer. The treatment of breast cancer has improved greatly in the last two decades. However, brain metastases from breast cancer remain the leading cause of morbidity and mortality. Patients with breast

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Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Breast cancer brain metastasis: Current evidence and future directions

Sun

Dai

et al. 2022

Cancer Medicine

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“…All TKIs are substrates of ABC transporters, limiting their brain accumulation at relevant concentrations [ 99 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. Using efflux transporter inhibitors might be a way to significantly enhance brain accumulations of anticancer drugs (reviewed in [ 25 ]), with promising preclinical data [ 97 , 129 , 130 , 131 , 132 , 133 ]. P-Gp inhibitors have failed in clinical trials.…”

Section: How To Reduce the Brain Efflux Of Anti-cancer Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…Indeed, diffusion into the brain parenchyma remains a pharmaceutical challenge because of the highly selective blood–brain barrier, combined with protective efflux systems limiting brain exposure to most xenobiotics, two important topics that our research team has recently reviewed in [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

Angeli

Bousquet

2021

Pharmaceutics

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The incidence of brain metastases has been increasing constantly for the last 20 years, because of better control of metastases outside the brain, and the failure of most drugs to cross the blood–brain barrier at relevant pharmacological concentrations. Recent advances in the molecular biology of cancer have led to the identification of numerous molecular alterations, some of them targetable with the development of specific targeted therapies, including tyrosine kinase inhibitors. In this narrative review, we set out to describe the state-of-the-art in the use of tyrosine kinase inhibitors for the treatment of melanoma, lung cancer, and breast cancer brain metastases. We also report preclinical and clinical pharmacological data on brain exposure to tyrosine kinase inhibitors after oral administration and describe the most recent advances liable to facilitate their penetration of the blood–brain barrier at relevant concentrations and limit their physiological efflux.

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“…However, signs of adverse effects were observed at high CSF concentrations of topotecan (0.4 mg). Therefore, as there are large individual differences in pharmacokinetics after intrathecal administration [ 1 , 23 , 24 , 25 ], both uniform regimen and personalized treatment development are required for the intrathecal administration of anticancer drugs. Thus, it is essential to establish and generalize the drug concentration monitoring system in the CSF.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection

Yoshikawa

Yamada

Yokota

et al. 2021

Cancers

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Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.

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The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

Cited by 5 publications

References 127 publications

Breast cancer brain metastasis: Current evidence and future directions

Breast cancer brain metastasis: Current evidence and future directions

Brain Metastasis Treatment: The Place of Tyrosine Kinase Inhibitors and How to Facilitate Their Diffusion across the Blood–Brain Barrier

Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection

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