James M Gallo

..Apoptosis-induced drug delivery offers a new avenue for targeted drug delivery research that uses biological control mechanisms...

..It is concluded that even in the neovasculature of brain tumors, Pgp has the facility to limit drug penetration, although somewhat less so than in normal brain...

..It is believed that this modeling strategy can be used as an aid in the drug development process by providing key insights into drug disposition in tumors and by offering a foundation to optimize drug regimen design...

..The method has the advantages of low sample volume, rapid clean-up, and the simultaneous measurement of MTX and 7-OH MTX in plasma and brain tissues allowing detailed PK studies to be completed in individual mice...

..Thus, the effect of the multitargeted tyrosine kinase inhibitor sunitinib on tumor distribution of temozolomide was investigated to evaluate conditions for optimal combination chemotherapy...

..In conclusion, the effect of sunitinib on the brain tumor distribution of TMZ was dose dependent and indicated that optimal tumor exposure was achieved at a lower dose and was associated with the VNI...

..In conclusion, several PK/PD factors contributing to the antitumor activity of the MD TMZ therapy have been identified and form a foundation for further investigations of low-dose TMZ regimens...

..It is proposed that the net balance of antiangiogenic drug-mediated pharmacodynamic actions will determine how drug disposition in tumors may be affected...

..The established method was successfully applied to the characterization of sunitinib disposition in the brain and brain tumor as well as its systemic pharmacokinetics in a murine orthotopic glioma model...

..The implementation of the PK/PD equivalent dosing strategy offers a new approach to drug development...

..Our goal was to show how the latter could be achieved for temozolomide, an agent used in the treatment of brain tumors, using an orthotopic brain tumor model in rats...

..Na, as a potential chemotherapeutic agent for brain tumors using a series of PK/PD studies, which led to the evaluation of its structural analog, ON013105, a prodrug of the more lipophilic product, ON013100...

..The novel concept of PK/PD equivalent dosing regimens could be applied in drug development and to delineate PG differences in drug activity...

..The findings confirmed that both Abcc2 and Abcc3 significantly influenced the PK properties of MTX, and depending on the MTX dose and strain, alternate elimination pathways were elicited and saturable...

..ON01910 exhibited a clearance of 3.61±0.85 l/h/kg and a half life of 8.66±3.30 h at 50 mg/kg dose given I.V...

..054 to 1.96 microg/ml in brain homogenates. A sensitive and specific assay for paclitaxel has been developed that has the advantages of using small sample sizes, and a single extraction step without solvent evaporation...

..This review will discuss insights into the physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 afforded by investigations of these new mouse models...

..01 to 1 microg/g in brain tissue. The advantage of the method enabled the quantitation of vincristine in multiple plasma samples obtained from a single mouse, which permitted the accurate estimation of its pharmacokinetic properties...

..07 to 2.5 microgram/ml, and from 0.03 to 1.3 microgram/ml in tumor homogenates. The main advantages of this method compared with earlier methods are the ability to measure intact carboplatin in a sensitive and specific manner...

..In both cases, the models performed well when analyzed in the context of the retrospective and bootstrap analyses. Prospective studies in ovarian cancer patients should be conducted to further tailor the current models...

..Four patients exhibited disease stability after two cycles of treatment. CP-461 is minimally toxic at doses up to 800 mg/day when administered p.o. on a twice-daily schedule...

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..This is the first demonstration that an ATP-binding cassette transporter can affect in vivo tissue sensitivity towards this class of agents...

..5 ± 0.20-fold variability in PD. The methods are sufficiently accessible and could be applied to other anticancer drugs and tumor models to obtain greater resolution of intratumoral PKs and PDs...

..To determine the maximum tolerated dose (MTD) of raltitrexed when given with irinotecan and to evaluate the pharmacokinetics of these two agents when given in combination...

..In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials...

..A plausible degradation pathway accounting for the available experimental data is presented...