Ahmed Hamed Salem, PhD, FCP

Adjunct Professor, Department of Experimental and Clinical Pharmacology (ECP)
Ahmed Hamed Salem

Contact

Titles

Adjunct Professor, Department of Experimental and Clinical Pharmacology (ECP)
Director, Clinical Development, Abbvie Inc.

Education

PhD, University of Minnesota Major: Experimental and Clinical Pharmacology, Minor: Biostatistics.

Bachelor of Pharmaceutical Sciences, Ain Shams University, Cairo, Egypt

Clinical Clerkship, North Memorial Health Hospital

Fellowships

Fellow of the American College of Clinical Pharmacology

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Biography

Awards & Recognition

  • AAPS Journal High Impact Article Award, American Association of Pharmaceutical Scientists Journal, 2018
  • Fellow of The American College of Clinical Pharmacology, Since 2017.
  • Five AbbVie Chairman’s and President’s Awards 2013-2019.
  • Pre-doctoral Fellowship in Clinical and Translational Research, Office of Clinical Research, University of Minnesota, 2008

Professional Associations

  • Chair of “Conducting Clinical Pharmacology & Bioavailability Studies of Targeted Anticancer Drugs in Healthy Subjects: Opportunities & Challenges Symposium” at the Annual Meeting of the American College of Clinical Pharmacology. Bethesda, MD 2018.
  • Chair of “Modeling & Simulation Strategies for Dose Selection of Targeted Anticancer Agents” Symposium at the Annual Meeting of the American College of Clinical Pharmacology. San Diego, CA 2017.
  • Invited Speaker at the FDA-organized Accelerating Anticancer Agent Development and Validation workshop. Bethesda, Maryland, 2017.
  • Member of the Publications Committee of the American College of Clinical Pharmacology since 2018.
  • Member of the STYP Committee of the American College of Clinical Pharmacology 2016-2018.
  • Member of the Publications committee of the International Society of Pharmacometrics (ISoP) since 2012.
  • Mentor for Young Professionals in the Industry/Regulatory Track in

Research Summary/Interests

Previous Projects with PhD Students

Chay Lim, University of Minnesota:

  • Chay Ngee Lim, Ahmed Hamed Salem. A Semi-Mechanistic Integrated Pharmacokinetic/Pharmacodynamic Model of the Testosterone Effects of the Gonadotropin-Releasing Hormone Agonist Leuprolide in Prostate Cancer Patients. Clinical Pharmacokinetics. 2015;54(9):963-73.

Ali AlHadab, University of Minnesota:

  • Ali A. Alhadab, Ahmed Hamed Salem, Kevin.J. Freise. A Semi-Mechanistic Model Of Ritonavir (RTV) CYP3A Inhibition And Pharmacokinetic (PK) Interaction With CYP3A Substrate Venetoclax (Ven). Clinical Pharmacology & Therapeutics. 2018;103(S1):PI-025, S22.
  • Ali A. Alhadab, Ahmed Hamed Salem, Kevin.J. Freise. Staggering Venetoclax (Ven) And Digoxin (Dig) Administration To Minimize Gastrointestinal P-gp Inhibition: A Model-Based Analysis. Clinical Pharmacology & Therapeutics. 2018;103(S1):PI-024, S21-S22.

Mengyao Li, Virginia Commonwealth University:

  • Mengyao Li, Ahmed Hamed Salem, Shekman L. Wong, Kevin J. Freise. Model‐Based Meta‐Analysis of Progression Free Survival (PFS) Time in Non‐Hodgkin’s Lymphoma (NHL) Patients. American College of Clinical Pharmacology Annual Meeting, September 25th – 27th, 2016 in Bethesda, MD.
  • Mengyao Li, Nimita Dave, Ahmed Hamed Salem, Kevin J. Freise. Model-Based Meta-Analysis of Progression-Free Survival in Non-Hodgkin's Lymphoma Patients. Medicine. Medicine. 2017 Sep;96(35):e7988. doi: 10.1097/MD.0000000000007988.

Naveen Mangal, University of Florida:

  • Naveen Mangal, Ahmed Hamed Salem, Rajeev Menon, Kevin J. Freise. Use of depth of response to predict progression-free survival in relapsed or refractory multiple myeloma: Evaluation of results from 102 clinical trials. Hematol Oncol. 2018 Apr 19. doi: 10.1002/hon.2514.
  • Suresh K. Agarwal, Naveen Mangal, Rajeev Menon, Kevin J. Freise, Ahmed Hamed Salem. Response Rates as Predictors of Overall Survival: A Meta-Analysis of Acute Myeloid Leukemia Trials. J Cancer 2017 Jun 3;8(9):1562-1567.
  • Naveen Mangal, Ahmed Hamed Salem, Mengyao Li, Rajeev Menon, Kevin J. Freise. Relationship Between Response Rates and Median Progression-Free Survival in Non-Hodgkin’s Lymphoma: A Meta-analysis of PublishedClinical Trials. Hematological Oncology. 2018 Feb;36(1):37-43. doi: 10.1002/hon.2463.
  • Naveen Mangal, Ahmed Hamed Salem, Rajeev Menon, Kevin J. Freise. Relationship Between Short-Term Response Rates and Long-Term Survival in Acute Myeloid Leukemia and Relapsed or Refractory Multiple Myeloma. American College of Clinical Pharmacology Annual Meeting, September 16th – 19th, 2017 in San Diego, CA.
  • Naveen Mangal, Ahmed Hamed Salem, Rajeev Menon, Kevin J. Freise. Relationship Between Short-Term Response Rates and Long-Term Survival in Acute Myeloid Leukemia and Relapsed or Refractory Multiple Myeloma. Blood 2016; 128:5128.

Abhinav Kurumaddali, University of Florida:

  • Abhinav Kurumaddali, Ahmed Hamed Salem, Suresh K. Agarwal. A Meta-Analysis of Higher-risk Myelodysplastic Syndrome Trials to Evaluate Relationship between Short-term Endpoints and Overall Survival. Journal of Cancer. Under Review.

Publications

Selected Publications

  • Ahmed Hamed Salem, Nimita Dave, Thomas Marbury, Beibei Hu, Dale Miles, Suresh K. Agarwal, Antoinette M. Sulpizi, Orlando F. Bueno, Rajeev M. Menon. Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Subjects with Hepatic Impairment. Clinical Pharmacokinetics. 2019 In Press.
  • Andrew H. Wei, Stephen A. Strickland Jr, Jing-Zhou Hou, Walter Fiedler, Tara L. Lin, Roland B. Walter, Anoop Enjeti, Ing Soo Tiong, Michael Savona, Sangmin Lee, Brenda Chyla, Relja Popovic, Ahmed Hamed Salem, Suresh Agarwal, Tu Xu, Kaffa M. Fakouhi, Rod Humerickhouse, Wan-Jen Hong, John Hayslip, Gail J. Roboz. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 In Press.
  • Aksana K. Jones, Ahmed Hamed Salem, Kevin J. Freise Power determination during drug development: Is optimizing the sample size based on exposure-response analyses underutilized? CPT: Pharmacometrics & Systems Pharmacology. DOI:10.1002/psp4.12380
  • Suresh K. Agarwal, Bo Tong, Orlando F. Bueno, Rajeev M. Menon, Ahmed Hamed Salem. Effect of Azithromycin on Venetoclax Pharmacokinetics in Healthy Volunteers: Implications for Dosing Venetoclax with P-gp Inhibitors. Adv Ther. 2018 Nov;35(11):2015-2023. doi: 10.1007/s12325-018-0793-y. Epub 2018 Sep 27.
  • Sven de Vos, Lode J. Swinnen, Ding Wang, Erin Reid, Nathan Fowler, Jaclyn Cordero, Martin Dunbar, Sari Heitner Enschede, Cathy Nolan, Adam M. Petrich, Jeremy A. Ross, Ahmed H. Salem, Maria Verdugo, Suresh Agarwal, Lang Zhou, Mark Kozloff, Loretta Nastoupil, and Christopher R. Flowers. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase 1b dose-finding study. Ann Oncol. 2018 Sep 1;29(9):1932-1938. doi: 10.1093/annonc/mdy256.
  • J. Scott Lee, Andrew Roberts, Dennis Juarez, Thanh-Trang T. Vo, Shruti Bhatt, Lee-or Herzog, Sharmila Mallya, Richard J. Bellin, Suresh K. Agarwal, Ahmed Hamed Salem, Tu Xu, Jai Jai, Lingxiao Li, John R. Hanna, Matthew S. Davids, Angela G. Fleischman, Susan O’Brien, Lloyd T., Lam, Joel D. Leverson, Anthony Letai, Jonathan H. Schatz, and David A. Fruman. Statins enhance efficacy of venetoclax in blood cancers. Science Translational Medicine 2018 Jun 13;10(445). pii: eaaq1240. doi: 10.1126/scitranslmed.aaq1240.
  • Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Peter Hillmen, John F. Seymour, Steven Coutre, Wojciech Jurczak, Stephen P. Mulligan, Anna Schuh, Sarit Assouline, Clemens-Martin Wendtner, Andrew W. Roberts, Matthew S. Davids, Johannes Bloehdorn, Talha Munir, Sebastian Böttcher, Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, Gary Gordon, Michael Hallek, William G. Wierda. Venetoclax for Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase 2 Pivotal Trial. J Clin Oncol. 2018 Jul 1;36(19):1973-1980. doi: 10.1200/JCO.2017.76.6840. Epub 2018 May 1.
  • Tommy T. Cheung, Ahmed Hamed Salem, Rajeev M. Menon, Wijith P. Munasinghe, Orlando F. Bueno, Suresh K. Agarwal. Pharmacokinetics of the BCL-2 inhibitor Venetoclax in Healthy Chinese Subjects. Clinical Pharmacology in Drug Development. 2018 May;7(4):435-440. doi: 10.1002/cpdd.395.
  • Apurvasena Parikh, Sathej Gopalakrishnan, Kevin J. Freise, Maria E. Verdugo, Rajeev M. Menon, Sven Mensing, Ahmed Hamed Salem. Exposure-Response Evaluations of Venetoclax Efficacy and Safety in Patients with Non-Hodgkin Lymphoma. Leukemia & Lymphoma. 2018 Apr;59(4):871-879. doi: 10.1080/10428194.2017.1361024.
  • Naveen Mangal, Ahmed Hamed Salem, Rajeev Menon, Kevin J. Freise. Use of depth of response to predict progression-free survival in relapsed or refractory multiple myeloma: Evaluation of results from 102 clinical trials. Hematol Oncol. 2018 Apr 19. doi: 10.1002/hon.2514.
  • Kevin J. Freise, Beibei Hu, Ahmed Hamed Salem. Impact of Ritonavir Dose and Schedule on CYP3A Inhibition and Venetoclax Clinical Pharmacokinetics. Eur J Clin Pharmacol. 2018 Apr;74(4):413-421. doi: 10.1007/s00228-017-2403-3.
  • Naveen Mangal, Ahmed Hamed Salem, Mengyao Li, Rajeev Menon, Kevin J. Freise. Relationship Between Response Rates and Median Progression-Free Survival in Non-Hodgkin’s Lymphoma: A Meta-analysis of PublishedClinical Trials. Hematological Oncology. 2018 Feb;36(1):37-43. doi: 10.1002/hon.2463.
  • Jeffrey Jones, Anthony R. Mato, William G. Wierda, Matthew S. Davids, Michael Choi, Bruce D. Cheson, Richard Furman, Nicole Lamanna, Paul M. Barr, Lang Zhou, Brenda Chyla, Ahmed Hamed Salem, Maria Verdugo, Rod A. Humerickhouse, Jalaja Potluri, Steven Coutre, Jennifer Woyach, John Byrd. Venetoclax for Chronic Lymphocytic Leukemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018 Jan;19(1):65-75. doi: 10.1016/S1470-2045(17)30909-9.
  • Kevin J. Freise, Aksana K. Jones, Maria E. Verdugo, Rajeev M. Menon, Paulo C. Maciag, Ahmed Hamed Salem.Moving beyond maximum tolerated dose for targeted oncology drugs: Use of clinical utility index to optimize venetoclax dosage in multiple myeloma patients. Clin Pharmacol Ther. 2017 Dec;102(6):970-976. doi: 10.1002/cpt.712.
  • Philippe Moreau, Asher Chanan-Khan, Andrew W. Roberts, Amit B. Agarwal, Thierry Facon, Shaji Kumar, Cyrille Touzeau, Elizabeth A. Punnoose, Jaclyn Cordero, Wijith Munasinghe, Jia Jia, Ahmed Hamed Salem, Kevin J. Freise, Joel D. Leverson, Sari Heitner Enschede, Jeremy A. Ross, Paulo C. Maciag, Maria Verdugo, Simon J. Harrison. Promising Efficacy and Acceptable Safety of Venetoclax Plus Bortezomib and Dexamethasone in Relapsed/ Refractory Multiple Myeloma. Blood. 2017 Nov 30;130(22):2392-2400. doi: 10.1182/blood-2017-06-788323.
  • Manoj S. Chiney, Rajeev M. Menon, Orlando Bueno, Bo Tong, Ahmed Hamed Salem. Clinical Evaluation of P-glycoprotein Inhibition by Venetoclax: A Drug Interaction Study with Digoxin. Xenobiotica. 2017 Oct 13:1-6. doi: 10.1080/00498254.2017.1381779.
  • Mengyao Li, Nimita Dave, Ahmed Hamed Salem, Kevin J. Freise. Model-Based Meta-Analysis of Progression-Free Survival in Non-Hodgkin's Lymphoma Patients. Medicine. Medicine. 2017 Sep;96(35):e7988. doi: 10.1097/MD.0000000000007988.
  • Ahmed Hamed Salem, Martin Dunbar, Suresh K. Agarwal. Pharmacokinetics of Venetoclax in Patients with 17p Deletion Chronic Lymphocytic Leukemia. Anti-Cancer Drugs. 2017 Sep;28(8):911-914. doi: 10.1097/CAD.0000000000000522.
  • Suresh K. Agarwal, Naveen Mangal, Rajeev Menon, Kevin J. Freise, Ahmed Hamed Salem. Response Rates as Predictors of Overall Survival: A Meta-Analysis of Acute Myeloid Leukemia Trials. J Cancer 2017 Jun 3;8(9):1562-1567.
  • Kevin J Freise, Mohamad Shebley, Ahmed Hamed Salem. Quantitative Prediction of the Effect of CYP3A Inhibitors and Inducers on Venetoclax Pharmacokinetics Using a Physiologically Based Pharmacokinetic Model. The Journal of Clinical Pharmacology. 2017 Jun;57(6):796-804. doi: 10.1002/jcph.858.
  • Suresh K Agarwal, Courtney D DiNardo, Jalaja Potluri, Martin Dunbar, Hagop M Kantarjian, Rod A Humerickhouse, Shekman L Wong, Rajeev M Menon, Marina Y Konopleva, Ahmed Hamed Salem. Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments. Clinical Therapeutics. 2017;39(2):359-67.
  • Ahmed Hamed Salem, Suresh K Agarwal, Martin Dunbar, Sari L Heitner Enschede, Rod A Humerickhouse, Shekman L Wong. Pharmacokinetics of Venetoclax, a Novel BCL‐2 Inhibitor, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non‐Hodgkin Lymphoma. The Journal of Clinical Pharmacology. 2017;57(4):484-92.
  • Kevin J Freise, Aksana K Jones, Doerthe Eckert, Sven Mensing, Shekman L Wong, Rod A Humerickhouse, Walid M Awni, Ahmed Hamed Salem. Impact of venetoclax exposure on clinical efficacy and safety in patients with relapsed or refractory chronic lymphocytic leukemia. Clinical Pharmacokinetics. 2017;56(5):515-23.
  • Matthew S Davids, Andrew W Roberts, John F Seymour, John M Pagel, Brad S Kahl, William G Wierda, Soham Puvvada, Thomas J Kipps, Mary Ann Anderson, Ahmed Hamed Salem, Martin Dunbar, Ming Zhu, Franklin Peale, Jeremy A. Ross, Lori Gressick, Monali Desai, Su Young Kim, Maria Verdugo, Rod A. Humerickhouse, Gary B. Gordon, John F. Gerecitano. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. Journal of Clinical Oncology. 2017;35(8):826-33.
  • Ahmed Hamed Salem, Beibei Hu, Kevin J Freise, Suresh K Agarwal, Dilraj S Sidhu, Shekman L Wong. Evaluation of the Pharmacokinetic Interaction between Venetoclax, a Selective BCL-2 Inhibitor, and Warfarin in Healthy Volunteers. Clinical Drug Investigation. 2017;37(3):303-9.
  • H. Liu, M. J. Michmerhuizen, Y. Lao, K. Wan, A. H. Salem, J. Sawicki, M. Serby, S. Vaidyanathan, S. L. Wong, S. Agarwal, M. Dunbar, J. Sydor, S. M. de Morais, A. J. Lee. Metabolism and Disposition of a Novel B-Cell Lymphoma-2 Inhibitor Venetoclax in Humans and Characterization of Its Unusual Metabolites. Drug Metabolism and Disposition. 2017;45(3):294-305.
  • Suresh K Agarwal, Ahmed Hamed Salem, Alexey V Danilov, Beibei Hu, Soham Puvvada, Martin Gutierrez, David Chien, Lionel D Lewis, Shekman L Wong. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL‐2 inhibitor, in patients with non‐Hodgkin lymphoma. British Journal of Clinical Pharmacology. 2017;83(4):846-54.
  • Ahmed Hamed Salem, Aksana Kaefer Jones, Marilia Santini-Oliveira, Graham P Taylor, Kristine B Patterson, Angela M Nilius, Cheri Enders Klein. No need for lopinavir dose adjustment during pregnancy: a population pharmacokinetic and exposure-response analysis in pregnant and nonpregnant HIV-infected subjects. Antimicrobial agents and chemotherapy. 2016;60(1):400-8.
  • Ahmed Hamed Salem, Suresh K Agarwal, Martin Dunbar, Silpa Nuthalapati, David Chien, Kevin J Freise, Shekman L Wong. Effect of Low‐and High‐Fat Meals on the Pharmacokinetics of Venetoclax, a Selective First‐in‐Class BCL‐2 Inhibitor. The Journal of Clinical Pharmacology. 2016;56(11):1355-61.
  • Marina Konopleva, Daniel A Pollyea, Jalaja Potluri, Brenda Chyla, Leah Hogdal, Todd Busman, Evelyn McKeegan, Ahmed Hamed Salem, Ming Zhu, Justin L Ricker. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discovery. 2016;6(10):1106-17.
  • Aksana K Jones, Kevin J Freise, Suresh K Agarwal, Rod A Humerickhouse, Shekman L Wong, Ahmed Hamed Salem. Clinical predictors of venetoclax pharmacokinetics in chronic lymphocytic leukemia and non-Hodgkin’s lymphoma patients: a pooled population pharmacokinetic analysis. The AAPS journal. 2016;18(5):1192-202.
  • Kevin J Freise, Aksana K Jones, Rajeev M Menon, Maria E Verdugo, Rod A Humerickhouse, Walid M Awni, Ahmed Hamed Salem. Relationship between venetoclax exposure, rituximab coadministration, and progression‐free survival in patients with relapsed or refractory chronic lymphocytic leukemia: demonstration of synergy. Hematological Oncology. 2016;doi: 10.1002/hon.2373.
  • Kevin J Freise, Martin Dunbar, Aksana K Jones, David Hoffman, Sari L Heitner Enschede, Shekman Wong, Ahmed Hamed Salem. Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure–response analysis. Cancer chemotherapy and pharmacology. 2016;78(4):847-53.
  • Suresh K Agarwal, Beibei Hu, David Chien, Shekman L Wong, Ahmed Hamed Salem. Evaluation of Rifampin's Transporter Inhibitory and CYP3A Inductive Effects on the Pharmacokinetics of Venetoclax, a BCL‐2 Inhibitor: Results of a Single‐and Multiple‐Dose Study. The Journal of Clinical Pharmacology. 2016;56(11):1335-43.
  • Ahmed Hamed Salem, Yi-Lin Chiu, Joaquin M Valdes, Angela M Nilius, Cheri E Klein. A novel ritonavir paediatric powder formulation is bioequivalent to ritonavir oral solution with a similar food effect. Antiviral therapy. 2015;20:425-32.
  • Chay Ngee Lim, Ahmed Hamed Salem. A Semi-Mechanistic Integrated Pharmacokinetic/Pharmacodynamic Model of the Testosterone Effects of the Gonadotropin-Releasing Hormone Agonist Leuprolide in Prostate Cancer Patients. Clinical pharmacokinetics. 2015;54(9):963-73.
  • Ahmed Hamed Salem, George G Zhanel, Safaa A Ibrahim, Ayman M Noreddin. Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit‐isolated methicillin‐resistant Staphylococcus aureus. Clinical and Experimental Pharmacology and Physiology. 2014;41(6):437-43.
  • Ahmed Hamed Salem, Jianning Yang, Alison Graham, Amita Patnaik, Kyle Holen, Rajendra Pradhan, Hao Xiong. Effect of Co-administration of Ketoconazole, a Strong CYP3A Inhibitor, on the Pharmacokinetics, Safety and Tolerability of Navitoclax, a First-in-class Oral Bcl-2 Family Inhibitor, in Cancer Patients. Anticancer Research. 2014;34(4):2001-6.
  • Ahmed H. Salem, Ayman M Noreddin. Moxifloxacin in lower respiratory tract infections: in silico simulation of different bacterial resistance and drug exposure scenarios. Journal of Chemotherapy. 2014;26(2):80-5.
  • Ahmed Hamed Salem, Denise Koenig, Dawn Carlson. Pooled population pharmacokinetic analysis of phase I, II and III studies of linifanib in cancer patients. Clinical pharmacokinetics. 2014;53(4):347-59.
  • Ahmed Hamed Salem, Vincent L Giranda, Nael M Mostafa. Population pharmacokinetic modeling of veliparib (ABT-888) in patients with non-hematologic malignancies. Clinical pharmacokinetics. 2014;53(5):479-88.
  • Ahmed Hamed Salem, Courtney V Fletcher, Richard C Brundage. Pharmacometric characterization of efavirenz developmental pharmacokinetics and pharmacogenetics in HIV-infected children. Antimicrobial agents and chemotherapy. 2014;58(1):136-43.
  • Boris Renjifo, Jean van Wyk, Ahmed Hamed Salem, Daniel Bow, Juki Ng, Michael Norton. Pharmacokinetic enhancement in HIV antiretroviral therapy: a comparison of ritonavir and cobicistat. AIDS reviews. 2014;17(1):37-46.
  • Ahmed H Salem, Walid F Elkhatib, Ayman M Noreddin. Pharmacodynamic assessment of vancomycin–rifampicin combination against methicillin resistant Staphylococcus aureus biofilm: a parametric response surface analysis. Journal of Pharmacy and Pharmacology. 2011;63(1):73-9.
  • Ahmed H Salem, Walid F Elkhatib, Ghada F Ahmed, Ayman M Noreddin. Pharmacodynamics of moxifloxacin versus vancomycin against biofilms of methicillin-resistant Staphylococcus aureus and epidermidis in an in vitro model. Journal of Chemotherapy. 2010;22(4):238-42.
  • Ayman M Noreddin, Walid F El-Khatib, Jason Aolie, Ahmed H Salem, George G Zhanel. Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible