Hirasawa, Makoto; Saleh, Mohammed A. A.; de Lange, Elizabeth C. M. published the artcile< The Extension of the LeiCNS-PK3.0 Model in Combination with the ""Handshake"" Approach to Understand Brain Tumor Pathophysiology>, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is brain tumor pathophysiol LeiCNS pharmacokinetic model drug development BBB; blood-tumor barrier; brain tumors; physiologically based pharmacokinetic model; tumor pathophysiology.
Micrometastatic brain tumor cells, which cause recurrence of malignant brain tumors, are often protected by the intact blood-brain barrier (BBB). Therefore, it is essential to deliver effective drugs across not only the disrupted blood-tumor barrier (BTB) but also the intact BBB to effectively treat malignant brain tumors. Our aim is to predict pharmacokinetic (PK) profiles in brain tumor regions with the disrupted BTB and the intact BBB to support the successful drug development for malignant brain tumors. LeiCNS-PK3.0, a comprehensive central nervous system (CNS) physiol. based pharmacokinetic (PBPK) model, was extended to incorporate brain tumor compartments. Most pathophysiol. parameters of brain tumors were obtained from literature and two missing parameters of the BTB, paracellular pore size and expression level of active transporters, were estimated by fitting existing data, like a “”handshake””. Simultaneous predictions were made for PK profiles in extracellular fluids (ECF) of brain tumors and normal-appearing brain and validated on existing data for six small mol. anticancer drugs. The LeiCNS-tumor model predicted ECF PK profiles in brain tumor as well as normal-appearing brain in rat brain tumor models and high-grade glioma patients within twofold error for most data points, in combination with estimated paracellular pore size of the BTB and active efflux clearance at the BTB. Our model demonstrated a potential to predict PK profiles of small mol. drugs in brain tumors, for which quant. information on pathophysiol. alterations is available, and contribute to the efficient and successful drug development for malignant brain tumors.
Pharmaceutical Research published new progress about Blood microvessel. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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