Charles Williams Flexner is an American

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

, clinical pharmaceutical scientist, academic, author and researcher. He is a Professor of Medicine at the

Johns Hopkins University School of Medicine The Johns Hopkins University School of Medicine (JHUSOM) is the medical school of Johns Hopkins University, a private research university in Baltimore, Maryland. Founded in 1893, the School of Medicine shares a campus with the Johns Hopkins Hospi ...

. Flexner's work is focused on the basic and

clinical pharmacology Clinical pharmacology has been defined as "that discipline that teaches, does research, frames policy, gives information and advice about the actions and proper uses of medicines in humans and implements that knowledge in clinical practice". Clinic ...

of drugs for

HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...

and related infections. He has published over 250 scientific manuscripts, reviews, and book chapters on the use of drugs for the treatment and prevention of HIV and other infectious diseases, this includes early studies of HIV protease inhibitors, and the use of accelerator mass spectrometry to determine drug disposition in humans. He has also authored several books and textbooks, including ''Protease Inhibitors in AIDS Therapy'', ''Integrative Pharmacology'', ''Antiretroviral Drug Interactions: A Practical Approach'', and ''2012 DDI: HIV Drug Interaction Guide.'' Flexner served as President of the ''American Federation for Medical Research (AFMR)'', and the ''AFMR Foundation''.

Education

Flexner received a B.S. degree in biology from

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...

in 1978, and his M.D. degree from the Johns Hopkins University School of Medicine in 1982. He then completed his internship and residency at Stanford University Hospital in 1985, and a laboratory fellowship with virologist

Bernard Moss Bernard Moss (born July 26, 1937 in Brooklyn) is a virologist at the National Institute of Allergy and Infectious Diseases, part of the United States National Institutes of Health. He is the Chief of the NIAID Laboratory of Viral Diseases and of ...

in the Laboratory of Viral Diseases at the

National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...

(NIAID) in 1988. In the following year, he served as a Clinical Fellow in Infectious Diseases and Clinical Pharmacology at the Johns Hopkins University School of Medicine.

Career

Following his clinical fellowship, Flexner held appointments as an Assistant Professor of Medicine and Assistant Professor of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine from 1989 until 1996. Along with these appointments, he also held a concurrent appointment as Assistant Professor of International Health at the Johns Hopkins University School of Hygiene and Public Health. In 1996, he was appointed as Associate Professor of Medicine, and Associate Professor of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine, and as Associate Professor of International Health at the Johns Hopkins University Bloomberg School of Public Health. In 2005, he was promoted to the position of Professor of Medicine and Professor of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine, and Professor of International Health at the Johns Hopkins University Bloomberg School of Public Health.

Research

Flexner's research currently focuses on the use of long-acting and extended-release drugs and formulations for the treatment and prevention of HIV and other infectious diseases, including

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

and

viral hepatitis Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...

. He participated in the discovery and clinical development of several new molecules and formulations for immediate-release and long-acting parenteral administration. He founded and directs the Long Acting/Extended Release Antiretroviral Research Resource Program (LEAP), In his studies regarding treatment of HIV, Flexner was an early advocate of use of ritonavir to enhance the pharmacokinetics of other drugs. He was also an early proponent of using the combination of the

integrase inhibitor Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, block ...

cabotegravir Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable Cabotegravir ...

, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form as an antiretroviral treatment option for people with HIV. As co-founder of the CADO Conferences, he has promoted the optimization of dose and formulation of antiretroviral drugs for more cost-efficient delivery in resource-limited settings. He also introduced drug development strategies for salvage therapy, and discussed the conflicts and solutions regarding this. In 2010, he studied age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir. Results of this study highlighted the potential importance of the pharmacokinetics and tolerability of antiretroviral drugs as the HIV-infected population ages; older individuals comprise an increasing proportion of people living with HIV and AIDS. Flexner examined human immunodeficiency virus type-1 tropism by conducting a comparative analysis between tropism assays using replication-competent virus and plasma-derived pseudotyped virions. He demonstrated the impact of low-dose ritonavir on the pharmacokinetics of the CXCR4 antagonist AMD070 in healthy volunteers, and found that AMD070 concentrations increased with concomitant ritonavir dosing.

Personal life

Flexner was born in 1956. He is the great-great nephew of the American educator

Abraham Flexner Abraham Flexner (November 13, 1866 – September 21, 1959) was an American educator, best known for his role in the 20th century reform of medical education, medical and higher education in the United States and Canada. After founding and direct ...

, and microbiologist

Simon Flexner Simon Flexner, M.D. (March 25, 1863 in Louisville, Kentucky – May 2, 1946) was a physician, scientist, administrator, and professor of experimental pathology at the University of Pennsylvania (1899–1903). He served as the first director of t ...

. He is also a cousin of Pulitzer Prize-winning historian

James Thomas Flexner James Thomas Flexner (January 13, 1908 – February 13, 2003) was an American historian and biographer best known for the four-volume biography of George Washington that earned him a National Book Award in Biography

Awards and honors

*1990 - Clinical Investigator Award, National Institute of Allergy and Infectious Diseases, NIH *1994 - Leon I. Goldberg Young Investigator Award, American Society for Clinical Pharmacology and Therapeutics *1995 - Pfizer Visiting Professor of Medicine and Clinical Pharmacology, Stanford University School of Medicine, Stanford, California. *2004 - M. Glenn Koeing Lecturer, Vanderbilt University School of Medicine *2006 - Joseph E. Murray Lecturer, American Association of Plastic Surgeons *2012 - Honorary Fellow Award, American College of Clinical Pharmacology

Bibliography

Books

*Protease Inhibitors in AIDS Therapy (2001) ISBN 9780824704612 *HIV Drug Interaction Guide DDI 2012: The Companion Guide to Medical Management of HIV Infection (2012) ISBN 9780983711179

Selected articles

*Flexner C, Tierney C, Gross R, Andrade A, Lalama C, Eshleman SH, Aberg J, Sanne I, Parsons T, Kashuba A, Rosenkranz SL, Kmack A, Ferguson E, Dehlinger M, Mildvan D, AIDS Clinical Trials Group A5073 Study Team (2010). Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naïve patients: results of AIDS Clinical Trials Group (ACTG) A5073, a 48-week randomized controlled trial. Clinical Infectious Diseases, 50, 1041–1052. MCID #2833234; NIHMS #168892*Bakshi, R. P., Hamzeh, F., Frank, I., Eron, J. J., Jr, Bosch, R. J., Rosenkranz, S. L., Cramer, Y. S., Ussery, M., & Flexner, C. (2007). Effect of hydroxyurea and dideoxyinosine on intracellular 3'-deoxyadenosine-5'-triphosphate concentrations in HIV-infected patients. AIDS Research and Human Retroviruses, 23(11), 1360–1365. *Crawford, K. W., Li, C., Keung, A., Su, Z., Hughes, M. D., Greaves, W., Kuritzkes, D., Gulick, R., Flexner, C., & ACTG A5211 Study Team (2010). Pharmacokinetic/pharmacodynamic modeling of the antiretroviral activity of the CCR5 antagonist vicriviroc in treatment experienced HIV-infected subjects (ACTG protocol 5211). Journal of Acquired Immune Deficiency Syndromes, 53(5), 598–605. *Rajoli, R., Flexner, C., Chiong, J., Owen, A., Donnelly, R. F., Larrañeta, E., & Siccardi, M. (2019). Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK. European Journal of Pharmaceutics and Biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 144, 101–109. *Rajoli, R., Curley, P., Chiong, J., Back, D., Flexner, C., Owen, A., & Siccardi, M. (2019). Predicting Drug-Drug Interactions Between Rifampicin and Long-Acting Cabotegravir and Rilpivirine Using Physiologically Based Pharmacokinetic Modeling. The Journal of Infectious Diseases, 219(11), 1735–1742. https://doi.org/10.1093/infdis/jiy726 *Phillips AN, Bansi-Matharu L, Cambiano V, Ehrenkranz P, Serenata C, Venter F, Pett S, Flexner C, Jahn A, Revill P, Garnett G. The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis (2021). Lancet Global Health, 9(5), e620-e627. doi: 10.1016/S2214-109X(21)00025-5.

References

{{DEFAULTSORT:Flexner, Charles American physicians Living people Stanford University alumni Johns Hopkins University alumni Johns Hopkins University faculty Year of birth missing (living people)