Abstract
The incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood–brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood.
Highlights
Since 1914 and the development of salvarsan to treat syphilis and its neurological damage, penetration of drugs into the brain has continued to be a pharmaceutical challenge [1]
We provide a summary of knowledge on drug penetration into the brain parenchyma after intracerebrospinal fluid injection and the different systems causing their efflux
The tracers exited the brain via para-venous routes of the medial internal cerebral veins and the lateral-ventral caudal rhinal veins. These results demonstrate that interstitial cerebral fluid and cerebrospinal fluid (CSF) circulate and are cleared via the same para-arterial and para-venous spaces in the glymphatic system
Summary
Since 1914 and the development of salvarsan to treat syphilis and its neurological damage, penetration of drugs into the brain has continued to be a pharmaceutical challenge [1]. Systemic anticancer treatments, including the classic chemotherapies and targeted treatments, have a limited benefit on cancer brain metastases because they do not readily cross the BBB, obtaining only insufficient pharmacological concentrations in the brain [2]. To overcome this problem, direct intrathecal injections of drugs have been proposed for the treatment of carcinomatosis meningitidis and parenchymal brain metastases [11,12]. We provide a summary of knowledge on drug penetration into the brain parenchyma after intracerebrospinal fluid injection and the different systems causing their efflux
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