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Dr. Petty's laboratory interests focuses on antimicrobial chemotherapy, hospital-based medical practices, and internal medicine collaboration with ophthalmologic clinical trials.
A. Laboratory activities include the use of accelerator mass spectrometry (AMS) techniques to measure intracellular drugs and drugs metabolites. AMS is a highly sensitive method for detecting tracer amounts of radio-labeled molecules in cells, tissues, and body fluids. We have been able to measure intracellular zidovudine triphosphate (the active anabolite of zidovudine) in peripheral blood mononuclear cells from healthy volunteers given small doses of 14C-zidovudine, and have directly compared the sensitivity of AMS to traditional LC/MS methods carried out in our laboratory.
B. Clinical research activities investigate the clinical pharmacology of new anti-HIV therapies and drug combinations. Specific drug classes studied include HIV reverse transcriptase inhibitors, protease inhibitors, entry inhibitors (selective CCR5 and CXCR4 antagonists), and integrase inhibitors. Scientific objectives of clinical studies include characterization of early drug activity, toxicity, and pharmacok...inetics. Additional objectives are characterization of pathways of drug metabolism, and identification of clinically significant harmful and beneficial drug interactions mediated by hepatic and intestinal cytochrome P450 isoforms. view more
Research in the Craig W. Hendrix Lab concentrates on the chemoprevention of HIV infection, clinical pharmacology of antiviral drugs, drug interactions, and oral, topical and injectable HIV microbicide development. Our lab conducts small, intensive sampling studies of PK and PD of drugs for HIV prevention with a focus on developing methods to better understand HIV and drug distribution in the male genital tract, female genital tract and lower gastrointestinal tract. We also support numerous HIV pre-exposure prophylaxis development studies from phase I to phase III, largely as leader of the Pharmacology Core Laboratory of both the Microbicide Trial Network and HIV Prevention Trials Network.
Research focuses on clinical pharmacology of new anti-tuberculosis regimens with an emphasis on: (1) Phase I clinical trials of new or existing anti-TB drugs including dose escalation trials and studies of drug-drug interactions between anti-TB agents and antiretrovirals to treat HIV; (2) Use of PK/PD analysis and modelling in Phase II tuberculosis clinical treatment trials to determine concentration-effect relationships that will allow for optimization of dosing; and (3) Evaluation of TB and HIV drug concentrations in special populations, such as pregnant women and children; (4) Evaluation of treatment-shortening regimens for drug-sensitive TB and investigational regimens for treatment of multidrug-resistant TB; and (5) Translational work involving novel animal models of cavitary pulmonary TB disease to understand drug distribution in diseased lung.
The Bumpus Laboratory uses mass spectrometry and molecular pharmacology-based approaches to study the biotransformation of clinically used drugs by the cytochromes P450s. Specifically, we are studying ways to define a role for cytochrome P450-dependent metabolites in the drug-induced acute liver failure that is associated with certain antiviral drugs used to treat HIV and hepatitis C. Our long-term goal is to gain information that can be used to develop therapies that are devoid of toxic events by preventing the formation of a toxic metabolite or by developing strategies for preventing toxicity using concomitant therapy.
The Theresa Shapiro Laboratory studies antiparasitic chemotherapy. On a molecular basis, we are interested in understanding the mechanism of action for existing antiparasitic agents, and in identifying vulnerable metabolic targets for much-needed, new, antiparasitic chemotherapy. Clinically, our studies are directed toward an evaluation, in humans, of the efficacy, pharmacokinetics, metabolism and safety of experimental antiparasitic drugs.
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