We currently have an active protocol for preclinical pharmacokinetic analysis of new agents, and a continued close working relationship with the Pharmacology and Experimental Therapeutics Section of the POB to partner in pharmacologic investigations of new agents. We have successfully obtained new agents from intramural and extramural sources to investigate, and are developing biomarkers in the preclinical setting. In general, for an antitumor agent to have an effect, you need: -an active agent, -Delivered to tumor -Present at tumor site in its active form -Effective concentrations -Long enough period of time -Tolerability at doses necessary to achieve above -For targeted therapy, need to know if the target is present We are developing methods to further investigate the mechanisms of action of agents currently in clinical trials, and investigate biomarkers or surrogate markers of drug activity and tumor response. We have developed a new animal model for brain microdialysis in an effort to determine if Cerebrospinal fluid penetration is an appropriate surrogate for CNS tissue penetration. We are also evaluating effects of common concurrent medications such as steroids on the pharmacokinetics of chemotherapeutic agents.
|League-Pascual, James C; Lester-McCully, Cynthia M; Shandilya, Shaefali et al. (2017) Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model. J Neurooncol 132:401-407|
|Shah, Nirali N; Cole, Diane E; Lester-McCully, Cynthia M et al. (2016) Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in Non-human primates. Invest New Drugs 34:61-5|
|Cole, Diane E; Lester-McCully, Cynthia M; Widemann, Brigitte C et al. (2015) Plasma and cerebrospinal fluid pharmacokinetics of the Akt inhibitor, perifosine, in a non-human primate model. Cancer Chemother Pharmacol 75:923-8|
|Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P et al. (2015) Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta). Comp Med 65:77-82|
|McCully, Cynthia M; Pastakia, Devang; Bacher, John et al. (2013) Model for concomitant microdialysis sampling of the pons and cerebral cortex in rhesus macaques (Macaca mulatta). Comp Med 63:355-60|
|Marcus, Leigh; Murphy, Robert; Fox, Elizabeth et al. (2012) The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates. Cancer Chemother Pharmacol 69:247-52|