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Article
Strategies to target drugs to gliomas and CNS metastases of solid tumors
The treatment for central nervous system metastases of solid tumors and gliomas is limited as the blood–brain barrier (BBB) is an obstacle to systemic therapy. Here, we review the physiochemical properties of ...
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Article
Cognitive impact of cytotoxic agents in mice
Adjuvant chemotherapy is associated with changes in cognition in a subgroup of cancer patients. Chemotherapy is generally given as a combination of cytotoxic agents, which makes it hard to define the agent res...
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Article
Chemotherapy-related cognitive dysfunction: current animal studies and future directions
Cognitive impairment is a potential long-term side effect of adjuvant chemotherapy that can have a major impact on the quality of life of cancer survivors. There is a growing number of preclinical studies addr...
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Article
Therapy-resistant tumor microvascular endothelial cells contribute to treatment failure in glioblastoma multiforme
Glioblastoma multiforme (GBM) is a devastating disease with high mortality and poor prognosis. Cancer stem cells (CSCs) have recently been defined as a fraction of tumor cells highly resistant to therapy and s...
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Article
Open AccessPaclitaxel in self-micro emulsifying formulations: oral bioavailability study in mice
The anticancer drug paclitaxel is formulated for i.v. administration in a mixture of Cremophor EL and ethanol. Its oral bioavailability is very low due to the action of P-glycoprotein in the gut wall and CYP45...
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Article
Disposition and toxicity of trabectedin (ET-743) in wild-type and mdr1 gene (P-gp) knock-out mice
Trabectedin is a novel anticancer drug active against soft tissue sarcomas. Trabectedin is a substrate for P-glycoprotein (P-gp), which is encoded by mdr1a/1b in rodents. Plasma and tissue distribution, and excre...
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Article
Open AccessCharacterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI
To enhance the success rate of antiangiogenic therapies in the clinic, it is crucial to identify parameters for tumour angiogenesis that can predict response to these therapies. In brain tumours, one such para...
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Article
Determination of oxaliplatin in human plasma and plasma ultrafiltrate by graphite-furnace atomic-absorption spectrometry
A method for sensitive determination of the anti-cancer agent oxaliplatin in human plasma and human plasma ultrafiltrate (pUF) is presented. The method is based on the quantification of platinum by graphite-fu...
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Article
Open AccessP-glycoprotein and Mrp1 collectively protect the bone marrow from vincristine-induced toxicity in vivo
ABC transporter proteins may protect haematopoietic progenitor cells from chemotherapy-induced toxicity. By using an in vitro colony-forming assay, we found that bone marrow of Mdr1ab, Mrp1, Mdr1ab/Mrp1 knockout ...
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Article
A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling
Abstract
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Article
Open AccessThe co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients
The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one ...
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Article
Validated method for the determination of the novel organo-ruthenium anticancer drug NAMI-A in human biological fluids by Zeeman atomic absorption spectrometry
NAMI-A is a novel ruthenium-containing experimental anticancer agent. We have developed and validated a rapid and sensitive analytical method to determine NAMI-A in human plasma, plasma ultrafiltrate and urin...
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Article
Open AccessPhase I trial and pharmacological study of a 3-hour paclitaxel infusion in children with refractory solid tumours: a SFOP study
The maximum tolerated dose of paclitaxel administered by 24-hour continuous infusion in children is known. Short infusion might offer equivalent antitumour efficacy and reduced haematological toxicity, without...
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Article
Open AccessCremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients
The non-linear plasma pharmacokinetics of paclitaxel in patients has been well established, however, the exact underlying mechanism remains to be elucidated. We have previously shown that the non-linear plasma...
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Article
Open AccessPhase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule
Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min IV infusion to 51 patients with advanc...
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Article
Pharmacokinetics and metabolism of the staurosporine analogue CGP 41 251 in mice
Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-α inhibitor, revealed that oral administration of 400 μg/day of the compound to wild type mice on four successive days reversed multi d...
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Article
Open AccessIncreased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein
To gain more insight into the pharmacological role of endogenous P-glycoprotein in the metabolism of the widely used substrate drug doxorubicin, we have studied the plasma pharmacokinetics, tissue distribution...
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Article
A clinical pharmacokinetics study of carzelesin given by short-term intravenous infusion in a phase I study
We investigated the pharmacokinetic behavior of carzelesin in 31 patients receiving this drug by 10-min intravenous infusion in a Phase I clinical trial, which was conducted at institutions in Nijmegen (insti...
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Article
Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC 833
Inhibition of intestinal P-glycoprotein might enhance the absorption of orally administered P-glycoprotein substrate drugs. We show here a 10-fold increased oral bioavailability of paclitaxel in mice treated w...
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Article
Oral Bioavailability of Low Dose (20mg) ‘Home-Made’ Etoposide Capsules
The oral bioavailability of etoposide 20mg capsules, which were manufactured in our hospital pharmacy, was studied in 14 patients with various types of solid tumours. The presence of the lubricant colloidal si...
