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Charles W. Flexner

Charles Flexner

Department Affiliation: Primary: Medicine; Secondary: Pharmacology and Molecular Sciences
Degree: M.D., Johns Hopkins University
Rank: Professor
Telephone Number: 410-955-9712
Fax Number: 410-955-9708
E-mail address: flex@jhmi.edu
School of Medicine Address: 575 Osler Building, 600 N. Wolfe St., Baltimore, MD 21287-5554

 

Basic and clinical pharmacology of  antiretroviral drugs; HIV protease inhibitors and entry inhibitors    

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 pharmacokinetics. 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.


Representative Publications:

  • Flexner C, Plumley B, Ripin DHB. Treatment optimization: an outline for future success. Current Opin HIV/AIDS 2013; 8: 523-527. Pub Med Reference
     
  • Adriana A, Rosenkranz SL, Cillo A, Lu D, Daar E, Jacobson JM, Lederman M, Acosta E, Read S, Campbell T, Feinberg J, Flexner C, Mellors JW, Kuritzkes DR, AIDS Clinical Trials Group A5248 Team. Three distinct phases of HIV-1 RNA decay in treatment-naïve patients receiving raltegravir-based antiretroviral therapy: ACTG A5248 study. J Infect Dis 2013; 208:884-891. Pub Med Reference not available
     
  • Williams J, Sayles HR, Meza JL, Sayre P, Sandkovsky U, Gendelman HE, Flexner C, Swindells S. Long-acting parenteral nanoformulated antiretroviral therapy: interest and attitudes of HIV-infected patients. Nanomedicine (Lond). 2013; in press. [April 23, 2013 Epub ahead of print] Pub Med Reference
     
  • Lee LS, Pham P, Flexner C. Unexpected drug-drug interactions in HIV therapy: induction of UGT1A1 and bile efflux transporters by efavirenz. Annals Acad Med (Singapore) 2012; 41: 559-562. Pub Med Reference
     
  • Chen J, Flexner C, Liberman RG, Skipper PL, Louissaint N, Tannenbaum SR, Hendrix CW, Fuchs EJ. Biphasic elimination of tenofovir diphosphate and nonlinear pharmacokinetics of zidovudine triphosphate in a microdosing study. J Acq Immunodef Syndr 2012; 61: 593-599. Pub Med Reference
     
  • Wang L, Soon GH, Seng K-Y, Li J, Lee E, Yong E-L, Goh B-C, Flexner C, Lee L.  Pharmacokinetic modeling of plasma and intracellular concentrations of raltegravir in healthy volunteers. Antimicrob Agents Chemother 2011; 55: 4090-4095. Pub Med Reference
     
  • Chen, J., Garner, R.C., Lee, L.S., Seymour, M., Fuchs, E.J., Hubbard, W., Parsons, T., Pakes, G.E., Fletcher, C.V., Flexner, C. Accelerator mass spectrometry measurement of intracellular concentrations of active drug metabolites in human target cells in vivo. Clin Pharmacol Ther 2010; 88:796-800. Pub Med Reference
     
  • Crawford, K.W., Li, C., Keung, A., Su, Z., Hughes, M.D., Greaves, W., Kuritzkes, D., Gulick, R., Flexner, C. for the ACTG A5211 Study Team.  Pharmacokinetic/ pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist vicriviroc in treatment-experienced HIV-infected patients.  J Acq Immunodef Syndr 2010; 53:598–605. Pub Med Reference
     
  • Tsibris, A.M.N., Korber, B., Arnaout, R., Russ, R., Lo, C.-C., Leitner, T., Gaschen, B., Theiler, J., Paredes, R., Su, Z., Hughes, M.D., Gulick, R.M., Greaves, W., Coakley, E., Flexner, C., Nusbaum, C., Kuritzkes, D.R. Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS ONE 2009; 4(5):e5683. Pub Med Reference
     
  • Lee, L.S., Soon, G.H., Shen, P., Yong, E.-L., Flexner, C., Pham, P. Darunavir/ritonavir and efavirenz exert differential effects on MRP1 transporter expression and function in healthy volunteers. Antiviral Ther 2010; 15:275-279. Pub Med Reference

Other graduate programs in which Dr. Flexner participates:

Graduate Training Program in Clinical Investigation

 
 
 
 
 
 

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