Charles Flexner

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. ncbi request reprint Current status and future prospects of therapeutic drug monitoring and applied clinical pharmacology in antiretroviral therapy
    Marta Boffito
    Chelsea and Westminster Hospital, London, UK
    Antivir Ther 10:375-92. 2005
  2. pmc Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir
    Adriana S A Andrade
    Division of Infectious Diseases, The Johns Hopkins University, Baltimore, MD 21287, USA
    BMC Complement Altern Med 8:50. 2008
  3. ncbi request reprint Tipranavir
    Charles Flexner
    Division of Clinical Pharmacology, Johns Hopkins University, Baltimore, Maryland 21287 5554, USA
    Nat Rev Drug Discov 4:955-6. 2005
  4. pmc Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial
    Charles Flexner
    Johns Hopkins University, Baltimore, Maryland, USA
    Clin Infect Dis 50:1041-52. 2010
  5. ncbi request reprint HIV drug development: the next 25 years
    Charles Flexner
    Johns Hopkins University, Divisions of Clinical Pharmacology and Infectious Diseases, Departments of Medicine, Pharmacology and Molecular Sciences, and International Health, Baltimore, Maryland 21287 5554, USA
    Nat Rev Drug Discov 6:959-66. 2007
  6. ncbi request reprint Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring
    Richard E Nettles
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Clin Infect Dis 42:1189-96. 2006
  7. ncbi request reprint Psychological distress and physical pain appear to have no short-term adverse impact on plasma HIV-1 RNA levels in patients on successful HAART
    Richard E Nettles
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 08543, USA
    HIV Clin Trials 6:262-71. 2005
  8. ncbi request reprint Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz
    Paul A Pham
    Johns Hopkins Hospital, Baltimore, MD, USA
    Antivir Ther 12:963-9. 2007
  9. pmc Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir
    Keith W Crawford
    Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    AIDS Res Hum Retroviruses 26:635-43. 2010
  10. ncbi request reprint Beneficial pharmacokinetic interaction between atazanavir and lopinavir/ritonavir
    Paul A Pham
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Acquir Immune Defic Syndr 45:201-5. 2007

Detail Information

Publications54

  1. ncbi request reprint Current status and future prospects of therapeutic drug monitoring and applied clinical pharmacology in antiretroviral therapy
    Marta Boffito
    Chelsea and Westminster Hospital, London, UK
    Antivir Ther 10:375-92. 2005
    ..In addition, the panel formulated a series of position statements that are relevant to the interpretation of current data and can aid the design of future clinical trials...
  2. pmc Pharmacokinetic and metabolic effects of American ginseng (Panax quinquefolius) in healthy volunteers receiving the HIV protease inhibitor indinavir
    Adriana S A Andrade
    Division of Infectious Diseases, The Johns Hopkins University, Baltimore, MD 21287, USA
    BMC Complement Altern Med 8:50. 2008
    ..We evaluated potential pharmacokinetic interactions between IDV and AG, and assessed whether AG improves IDV-induced insulin resistance...
  3. ncbi request reprint Tipranavir
    Charles Flexner
    Division of Clinical Pharmacology, Johns Hopkins University, Baltimore, Maryland 21287 5554, USA
    Nat Rev Drug Discov 4:955-6. 2005
  4. pmc Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial
    Charles Flexner
    Johns Hopkins University, Baltimore, Maryland, USA
    Clin Infect Dis 50:1041-52. 2010
    ..The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level <200 copies/mL) through week 48...
  5. ncbi request reprint HIV drug development: the next 25 years
    Charles Flexner
    Johns Hopkins University, Divisions of Clinical Pharmacology and Infectious Diseases, Departments of Medicine, Pharmacology and Molecular Sciences, and International Health, Baltimore, Maryland 21287 5554, USA
    Nat Rev Drug Discov 6:959-66. 2007
    ....
  6. ncbi request reprint Marked intraindividual variability in antiretroviral concentrations may limit the utility of therapeutic drug monitoring
    Richard E Nettles
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Clin Infect Dis 42:1189-96. 2006
    ..Effective therapeutic drug monitoring for antiretrovirals requires a better understanding of intraindividual variability in pharmacokinetics...
  7. ncbi request reprint Psychological distress and physical pain appear to have no short-term adverse impact on plasma HIV-1 RNA levels in patients on successful HAART
    Richard E Nettles
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 08543, USA
    HIV Clin Trials 6:262-71. 2005
    ..However, the short-term effect of psychological and physical distress on HIV-1 RNA levels in patients on successful HAART has not been well studied...
  8. ncbi request reprint Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz
    Paul A Pham
    Johns Hopkins Hospital, Baltimore, MD, USA
    Antivir Ther 12:963-9. 2007
    ..Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions...
  9. pmc Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir
    Keith W Crawford
    Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    AIDS Res Hum Retroviruses 26:635-43. 2010
    ..Age-related changes in the pharmacokinetics of antiretroviral drugs may be of increasing importance as the HIV-infected population ages and as older individuals comprise an increasing proportion of new diagnoses...
  10. ncbi request reprint Beneficial pharmacokinetic interaction between atazanavir and lopinavir/ritonavir
    Paul A Pham
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Acquir Immune Defic Syndr 45:201-5. 2007
    ..Because these agents, to various degrees, are substrates, inducers, and inhibitors of CYP450 3A4, there is concern for alterations in the pharmacokinetics (PK) of these combined agents...
  11. doi request reprint Possible differential induction of phase 2 enzyme and antioxidant pathways by american ginseng, Panax quinquefolius
    Lawrence S Lee
    Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
    J Clin Pharmacol 48:599-609. 2008
    ..79; 0.72-0.86; P < .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative stress markers...
  12. pmc Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248
    Adriana Andrade
    The Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Infect Dis 208:884-91. 2013
    ..The goal of this study was to define viral kinetics after initiation of raltegravir (RAL)-based antiretroviral therapy (ART)...
  13. doi request reprint Induction of chemoprotective phase 2 enzymes by ginseng and its components
    Lawrence S Lee
    Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
    Planta Med 75:1129-33. 2009
    ..The most potent inducing red ginseng extract also had the highest panaxytriol content, 120.8 microg/g. We found that ginseng induced NQO1 and that polyacetylenes are the most active components...
  14. pmc Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist Vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211)
    Keith W Crawford
    Department of Clinical Pharmacology, Johns Hopkins University, Baltimore, MD 21287, USA
    J Acquir Immune Defic Syndr 53:598-605. 2010
    ..This substudy of AIDS Clinical Trials Group (ACTG) Protocol 5211 explored the relationship between antiretroviral effect and plasma concentrations of vicriviroc, an investigational CCR5 antagonist for HIV infection...
  15. doi request reprint Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects
    Kelly E Dooley
    Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    J Acquir Immune Defic Syndr 62:21-7. 2013
    ..This study evaluated the effect of RIF or rifabutin (RBT) on the pharmacokinetics of the investigational HIV integrase inhibitor, dolutegravir (DTG)...
  16. pmc Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267
    Kelly E Dooley
    Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    J Acquir Immune Defic Syndr 59:455-62. 2012
    ..Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz...
  17. pmc Biphasic elimination of tenofovir diphosphate and nonlinear pharmacokinetics of zidovudine triphosphate in a microdosing study
    Jianmeng Chen
    Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    J Acquir Immune Defic Syndr 61:593-9. 2012
    ..To evaluate the prediction of microdosing for active intracellular drug metabolites, we compared the PK profile of 2 antiretroviral drugs, zidovudine (ZDV) and tenofovir (TFV), in microdose and standard dosing regimens...
  18. ncbi request reprint Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART
    Richard E Nettles
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    JAMA 293:817-29. 2005
    ....
  19. pmc Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations
    Kelly Dooley
    Divisions of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland 21231, USA
    Antimicrob Agents Chemother 52:4037-42. 2008
    ..Changes consistent with rifapentine autoinduction of metabolism were seen. Adverse reactions in two subjects may have represented rifamycin hypersensitivity syndrome, although some features were atypical...
  20. doi request reprint Drug interactions involving combination antiretroviral therapy and other anti-infective agents: repercussions for resource-limited countries
    Kelly E Dooley
    Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Infect Dis 198:948-61. 2008
  21. ncbi request reprint Steady-state pharmacokinetic interaction of modified-dose indinavir and rifabutin
    Fayez M Hamzeh
    Johns Hopkins Hospital, Johns Hopkins University, Osler 527, 600 N Wolfe Street, Baltimore, MD 21287 5554, USA
    Clin Pharmacol Ther 73:159-69. 2003
    ..Therefore this study was designed to evaluate alternative dosing regimens...
  22. pmc Multiple-dose escalation study of the safety, pharmacokinetics, and biologic activity of oral AMD070, a selective CXCR4 receptor inhibitor, in human subjects
    Nimalie D Stone
    Johns Hopkins University School of Medicine, Division of Clinical Pharmacology, Harvey 502, 600 N Wolfe Street, Baltimore, MD 21287, USA
    Antimicrob Agents Chemother 51:2351-8. 2007
    ..Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro 90% effective concentration of AMD070...
  23. doi request reprint Emerging antiretroviral drug interactions
    Paul A Pham
    Division of Infectious Diseases, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA
    J Antimicrob Chemother 66:235-9. 2011
    ..g. darunavir, raltegravir, maraviroc and etravirine)...
  24. pmc Use of antineoplastic agents in patients with cancer who have HIV/AIDS
    Michelle A Rudek
    Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Lancet Oncol 12:905-12. 2011
    ..We will review potential pharmacological interactions between antiretroviral and antineoplastic therapies and consider how to combine antiretroviral and antineoplastic agents in patients with HIV who are receiving HAART therapy...
  25. ncbi request reprint Effect of hydroxyurea and dideoxyinosine on intracellular 3'-deoxyadenosine-5'-triphosphate concentrations in HIV-infected patients
    Rahul P Bakshi
    Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA
    AIDS Res Hum Retroviruses 23:1360-5. 2007
    ..Since a significant reduction in dATP was measurable only when ddI was combined with HU, the antiretroviral activity of ddI may be more complex than previously assumed...
  26. doi request reprint Optimising the manufacture, formulation, and dose of antiretroviral drugs for more cost-efficient delivery in resource-limited settings: a consensus statement
    Keith W Crawford
    Johns Hopkins University, School of Medicine, Division of Clinical Pharmacology, Baltimore, MD, USA
    Lancet Infect Dis 12:550-60. 2012
    ..Optimising pharmacoenhancement and extending shelf life are additional strategies. The conference highlighted a range of interventions; optimum cost savings could be achieved through combining approaches...
  27. ncbi request reprint Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects
    Lawrence S Lee
    Division of Clinical Pharmacology, Johns Hopkins University, Baltimore, MD, USA
    Clin Infect Dis 43:1052-9. 2006
    ..Before recommending the use of NHPs as adjuncts to ARV use, studies should first exclude significant pharmacokinetic interactions and ensure that ARV efficacy is maintained...
  28. ncbi request reprint Optimization and simplification of antiretroviral therapy for adults and children
    Nathan Ford
    aHIV AIDS Department, World Health Organization, Geneva, Switzerland bDepartments of Medicine, Pharmacology, and International Health, Johns Hopkins University, Baltimore, Maryland, USA cDepartment of Pharmacological Research and Medicines Evaluation, Istituto Superiore di Sanita, Rome, Italy dClinton Health Access Initiative, Boston, USA
    Curr Opin HIV AIDS 8:591-9. 2013
    ..The review reflects on opportunities and challenges for HIV treatment optimization for the next 5 years...
  29. ncbi request reprint Treatment optimization: an outline for future success
    Charles Flexner
    aJohns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland bPangaea Global AIDS Foundation, Oakland, California cClinton Health Access Initiative, Boston, Massachusetts, USA
    Curr Opin HIV AIDS 8:523-7. 2013
    ..In this introduction, we outline current goals and approaches that will be described in more detail elsewhere in this issue...
  30. ncbi request reprint The antiretroviral drug pipeline: prospects and implications for future treatment research
    Charles Flexner
    aJohns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland bUniversity of Alabama at Birmingham, Birmingham, Alabama, USA
    Curr Opin HIV AIDS 8:572-8. 2013
    ..A number of investigational antiretroviral drugs in clinical development could alter the future treatment landscape for resource-limited settings and contribute to optimized therapy for HIV infection...
  31. ncbi request reprint Differential effects of p-glycoprotein and multidrug resistance protein-1 on productive human immunodeficiency virus infection
    R Renae Speck
    Department of Clinical Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Infect Dis 186:332-40. 2002
    ..These results suggest that the inhibition of HIV productive infection by P-gp and augmentation by MRP-1 occur predominantly at a preintegration step but act through different mechanisms...
  32. pmc In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject
    Athe M N Tsibris
    Massachusetts General Hospital, Boston, Massachusetts, USA
    J Virol 82:8210-4. 2008
    ..Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs...
  33. ncbi request reprint Pharmacology and drug interactions: a progress report
    Adriana Andrade
    Hopkins HIV Rep 14:8-9. 2002
  34. ncbi request reprint Effect of simultaneous versus staggered dosing on pharmacokinetic interactions of protease inhibitors
    Carla B Washington
    Department of Medicine, Stanford University Medical Center, Stanford, CA 94305 5130, USA
    Clin Pharmacol Ther 73:406-16. 2003
    ..The aim of this study was to determine whether pharmacokinetic interactions between the protease inhibitors saquinavir soft gel, nelfinavir, and ritonavir are affected by the timing of administration...
  35. ncbi request reprint Progress in pharmacology and drug interactions from the 10th CROI
    Adriana Andrade
    Hopkins HIV Rep 15:7, 11. 2003
  36. ncbi request reprint Update from the 6th International Workshop on the Clinical Pharmacology of HIV Therapy: new drugs, new formulations and drug interactions
    Charles Flexner
    Hopkins HIV Rep 17:1-3, 10-1. 2005
  37. ncbi request reprint Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307
    Ian Frank
    AIDS Res Hum Retroviruses 20:916-26. 2004
    ..HU may continue to have a role as a component of HIV therapy...
  38. ncbi request reprint Simplifying antiretroviral therapy
    Michael L Tapper
    New York University School of Medicine, New York, USA
    AIDS Read 14:355-60, 367-71. 2004
    ..Additional studies should add to this experience and provide guidance on the role and timing of such regimens in the management of patients with HIV disease...
  39. ncbi request reprint Genes, ethnicity, and efavirenz response: clinical pharmacology update from the 11th CROI
    Adriana Andrade
    Hopkins HIV Rep 16:1-7. 2004
  40. ncbi request reprint Drug development strategies for salvage therapy: conflicts and solutions
    Victor De Gruttola
    Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    AIDS Res Hum Retroviruses 22:1106-9. 2006
  41. ncbi request reprint Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211
    Roy M Gulick
    Weill Medical College of Cornell University, New York, New York, NY, USA
    J Infect Dis 196:304-12. 2007
    ..Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study...
  42. ncbi request reprint High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: efficacy, safety, and predictors of response
    Daniel Podzamczer
    Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain
    HIV Clin Trials 8:193-204. 2007
    ..To investigate the efficacy and safety of high-dose lopinavir/ritonavir (LPV/r) therapy in multiple protease inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced subjects...
  43. ncbi request reprint Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs
    Marta Boffito
    Chelsea and Westminster Hospital, London, UK
    Antivir Ther 10:469-77. 2005
    ....
  44. ncbi request reprint Model-based analysis of the pharmacokinetic interactions between ritonavir, nelfinavir, and saquinavir after simultaneous and staggered oral administration
    Jian feng Lu
    Department of Biopharmaceutical Sciences, University of California San Francisco, San Francisco, California 94143 0626, USA
    Drug Metab Dispos 30:1455-61. 2002
    ....
  45. ncbi request reprint Pharmacology at the 12th CROI: generic antiretrovirals, drug interactions, and therapeutic drug monitoring
    Adriana Andrade
    Hopkins HIV Rep 17:6-9. 2005
  46. ncbi request reprint Selected topics from the 9th Conference on Retroviruses and Opportunistic Infections
    Richard E Chaisson
    HIV Clin Trials 3:333-49. 2002
  47. ncbi request reprint HLA B57 and abacavir hypersensitivity
    Charles Flexner
    Hopkins HIV Rep 14:5. 2002
  48. ncbi request reprint IQs, VIQs, and NIQs: are we smart yet?
    Charles Flexner
    Hopkins HIV Rep 14:6-7. 2002
  49. ncbi request reprint More from CROI...new drugs: full pipeline, steady progress
    Charles Flexner
    Hopkins HIV Rep 15:4-5. 2003
  50. ncbi request reprint A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome
    Constance A Benson
    Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA
    Clin Infect Dis 37:1234-43. 2003
    ..057). Subjects in the C+E+R group had improved survival, compared with the C+E group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.83) and the C+R group (HR, 0.49; 95% CI, 0.26-0.92)...
  51. ncbi request reprint Diarrhea-associated HIV-1 APIs potentiate muscarinic activation of Cl- secretion by T84 cells via prolongation of cytosolic Ca2+ signaling
    Paul A Rufo
    GI Cell Biology, Combined Program in Pediatric Gastroenterology and Nutrition, Children s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
    Am J Physiol Cell Physiol 286:C998-C1008. 2004
    ..These data show that APIs modulate Ca(2+) signaling in secretory epithelial cells and identify a novel target for treatment of clinically important API side effects...
  52. ncbi request reprint Report from Boston: the 12th Conference on Retroviruses and Opportunistic Infections (CROI). New drugs, new targets: good news on the horizon
    Charles Flexner
    Hopkins HIV Rep 17:8-9. 2005
  53. ncbi request reprint HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211
    Timothy J Wilkin
    Division of International Medicine and Infectious Diseases, Weill Cornell Medical College, New York, NY, USA
    Clin Infect Dis 44:591-5. 2007
    ..Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors...
  54. ncbi request reprint New drugs: attacking chemokine receptors
    Charles Flexner
    Hopkins HIV Rep 14:12. 2002