Bernd Meibohm, PhD, FCP
Professor and Associate Dean for Research and Graduate Programs
444 Pharmacy Building
- Ph.D., Tech.Univ. Carolo-Wilhelmina, Braunschweig, Germany, Pharmaceutical Sciences
- B.S., Tech.Univ. Carolo-Wilhelmina, Braunschweig, Germany, Pharmacy
Dr. Meibohm’s research is focused on the investigation of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs with special emphasis on PK/PD-correlations.
Pharmacokinetic/pharmacodynamic (PK/PD)-modeling bridges the gap between dynamic dose-concentration relationships and static concentration-effect relationships of drugs. By combining information provided by pharmacokinetics and by pharmacodynamics, it facilitates the description and prediction of the time course of drug effects that are resulting from a certain dosing regimen. The application of these PK/PD-modeling concepts has been identified as beneficial in all phases of preclinical and clinical drug development as well as in applied clinical pharmacotherapy, where it provides a more rational basis for patient-specific dosage individualization.
Thus, the ultimate goal of the research in Dr. Meibohm’s lab is to contribute to the optimization of dosing regimens for increased efficacy and reduced toxicity and to modulate pharmacotherapy according to the needs of the individual patient.
Special areas of interest are:
- Pharmacokinetics and pharmacodynamics of cardiovascular and anesthetic drugs in pediatric patients and their dependency on developmental changes.
- Pharmacokinetics and pharmacodynamics of therapeutics for asthma and chronic obstructive pulmonary disease (COPD), with focus on corticosteroids and other anti-inflammatory agents.
- Application of pharmacometrics and quantitative pharmacology concepts in preclinical and clinical drug development
This includes the application of the following research techniques:
- Evaluation of the pharmacokinetic properties of investigational as well as marketed drugs or dosage forms in animal models, healthy volunteers or various patient subpopulations.
- Participation in the planning, conduct, and analysis of clinical trials.
- Development and validation of bioanalytical assays to quantify drug concentrations in biological fluids.
- Application of molecular biology research techniques for DNA, RNA and protein analysis relevant to drug response.
- Identification and validation of surrogate endpoints as measure for the pharmacologic activity of drugs.
- Computer-based mathematical modeling and simulation of the correlation between the pharmacokinetics and pharmacodynamics of drugs (PK/PD-modeling).
- Application of population approaches in pharmacokinetic and pharmacodynamic data analysis.
Dr. Meibohm’s research group is actively collaborating with researchers and clinicians at the University of Tennessee Colleges of Pharmacy, Medicine and Nursing, LeBonheur Children''s Medical Center, Memphis, TN, St. Jude Children''s Research Hospital, Memphis, TN, The Children''s Hospital of Philadelphia, Philadelphia, PA, Wake Forest University Medical Center, Winston-Salem, NC, the University of Düsseldorf School of Pharmacy, Düsseldorf, Germany, Metrum Institute, Augusta, ME, the Institute for Applied Healthcare Sciences, Hamburg, Germany, and in the pharmaceutical industry.
Current collaborative research projects include:
- Evaluation of the effect of developmental changes on the disposition of and response to investigational and clinically used drugs in pediatric patients, with specific focus on hepatic drug transporters.
- Investigation of the pharmacokinetics and pharmacodynamics of medications used in neonatal and pediatric pharmacotherapy, including population PK/PD modeling and simulation to optimize dosing strategies and trial designs.
- Pharmacokinetic and pharmacodynamic characterization including PK/PD-modeling of the investigational drugs, especially biotechnologically derived drug products.
- Preclinical pharmacokinetic and pharmacodynamic evaluation and optimization of novel anti-infectives against tuberculosis.
- Pharmacokinetic and pharmacodynamic evaluation of therapeutic proteins and their mechanisms of disposition and elimination.
Inflammatory Lung Disease
- Evaluation of the effect of genetic variations on the prevalence, severity, and pharmacotherapy of inflammatory pulmonary diseases, e.g. chronic obstructive pulmonary disease (COPD).
- Identification and validation of biomarkers for pulmonary decline
- Gene expression profiling for the identification of biomarkers for inflammation, disease progression and response to pharmacotherapeutic intervention in obstructive lung disease.
Quantitative Systems Pharmacology
Nonlinear mixed effects modeling
Modeling & simulation
- Della Casa Alberighi, O, Barrett, JS, LÃ¤er, S, Meibohm, B. Response to &quot;Physiologically based pharmacokinetic modeling at the extremes of age&quot;. Clin Pharmacol Ther, 93 (2), 149, 2013.
- Thudium, K, Bilic, S, Leipold, D, Mallet, W, Kaur, S, Meibohm, B, Erickson, H, Tibbitts, J, Zhao, H, Gupta, M. American Association of Pharmaceutical Scientists National Biotechnology Conference Short Course: Translational Challenges in Developing Antibody-Drug Conjugates: May 24, 2012, San Diego, CA. MAbs, 5 (1), 5-12, 2013.
- Bai, JP, Barrett, JS, Burckart, GJ, Meibohm, B, Sachs, HC, Yao, L. Strategic Biomarkers for Drug Development in Treating Rare Diseases and Diseases in Neonates and Infants. AAPS J, 2013.
- Rakesh, , Bruhn, D, Madhura, DB, Maddox, M, Lee, RB, Trivedi, A, Yang, L, Scherman, MS, Gilliland, JC, Gruppo, V, McNeil, MR, Lenaerts, AJ, Meibohm, B, Lee, RE. Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties. Bioorg Med Chem, 20 (20), 6063-72, 2012.
- van den Borst, B, Gosker, HR, Koster, A, Yu, B, Kritchevsky, SB, Liu, Y, Meibohm, B, Rice, TB, Shlipak, M, Yende, S, Harris, TB, Schols, AM, ,. The influence of abdominal visceral fat on inflammatory pathways and mortality risk in obstructive lung disease. Am J Clin Nutr, 96 (3), 516-26, 2012.
- Barrett, JS, Della Casa Alberighi, O, LÃ¤er, S, Meibohm, B. Physiologically based pharmacokinetic (PBPK) modeling in children. Clin Pharmacol Ther, 92 (1), 40-9, 2012.
- Chirmule, N, Jawa, V, Meibohm, B. Immunogenicity to Therapeutic Proteins: Impact on PK/PD and Efficacy. AAPS J, 14 (2), 296-302, 2012.
- Mehrotra, N, Tang, L, Phelps, SJ, Meibohm, B. Evaluation of vancomycin dosing regimens in preterm and term neonates using monte carlo simulations. Pharmacotherapy, 32 (5), 408-19, 2012.
- Kelmer, G, Bell, GC, Martin-Jimenez, T, Saxton, AM, Catasus, C, Elliot, SB, Meibohm, B. Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses. J Vet Pharmacol Ther, 2012.
- Bentley, AR, Kritchevsky, SB, Harris, TB, Newman, AB, Bauer, DC, Meibohm, B, Clark, AG, Cassano, PA, ,. Genetic variation in antioxidant enzymes and lung function. Free Radic Biol Med, 52 (9), 1577-1583, 2012.
- Swanson, JM, Wood, GC, Xu, L, Tang, LE, Meibohm, B, Homayouni, R, Croce, MA, Fabian, TC. Developing a gene expression model for predicting ventilator-associated pneumonia in trauma patients: a pilot study. PLoS One, 7 (8), e42065, 2012.
- Aldrich, MC, Kumar, R, Colangelo, LA, Williams, LK, Sen, S, Kritchevsky, SB, Meibohm, B, Galanter, J, Hu, D, Gignoux, CR, Liu, Y, Harris, TB, Ziv, E, Zmuda, J, Garcia, M, Leak, TS, Foreman, MG, Smith, LJ, Fornage, M, Liu, K, Burchard, EG, ,. Genetic ancestry-smoking interactions and lung function in African Americans: a cohort study. PLoS One, 7 (6), e39541, 2012.
- Meibohm, B, Zhou, H. Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol, 52 (1 Suppl), 54S-62S, 2012.
- Budha, NR, Kovar, A, Meibohm, B. Comparative performance of cell life span and cell transit models for describing erythropoietic drug effects. AAPS J, 13 (4), 650-61, 2011.
- Meibohm, B. Population pharmacokinetic/pharmacodynamic analyses as the basis for dosing of therapeutic monoclonal antibodies. Clin Pharmacokinet, 50 (12), 823-4, 2011.
- van den Borst, B, Koster, A, Yu, B, Gosker, HR, Meibohm, B, Bauer, DC, Kritchevsky, SB, Liu, Y, Newman, AB, Harris, TB, Schols, AM. Is age-related decline in lean mass and physical function accelerated by obstructive lung disease or smoking. Thorax, 66 (11), 961-9, 2011.
- Prado, ME, Ryman, JT, Boileau, MJ, Martin-Jimenez, T, Meibohm, B. Pharmacokinetics of ponazuril after oral administration to healthy llamas (Lama glama). Am J Vet Res, 72 (10), 1386-9, 2011.
- LÃ¤er, S, Meibohm, B. Study design and simulation approach. Handb Exp Pharmacol, 205, 125-48, 2011.
- Bai, JP, Bell, R, Buckman, S, Burckart, GJ, Eichler, HG, Fang, KC, Goodsaid, FM, Jusko, WJ, Lesko, LL, Meibohm, B, Patterson, SD, Puig, O, Smerage, JB, Snider, BJ, Wagner, JA, Wang, J, Walton, MK, Weiner, R. Translational biomarkers: from preclinical to clinical a report of 2009 AAPS/ACCP Biomarker Workshop. AAPS J, 13 (2), 274-83, 2011.
- Vaddady, PK, Mehrotra, N, Zhang, X, Yates, CR, Moore, BM, Meibohm, B. Pharmacokinetics of a combination of Δ9-tetrahydro-cannabinol and celecoxib in a porcine model of hemorrhagic shock. Biopharm Drug Dispos, 32 (2), 89-98, 2011.
- Dirks, NL, Meibohm, B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet, 49 (10), 633-59, 2010.
- Chen, J, Wang, Z, Li, CM, Lu, Y, Vaddady, PK, Meibohm, B, Dalton, JT, Miller, DD, Li, W. Discovery of Novel 2-Aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents. J Med Chem, 53 (20), 7414-27, 2010.
- Romero, K, Corrigan, B, Tornoe, CW, Gobburu, JV, Danhof, M, Gillespie, WR, Gastonguay, MR, Meibohm, B, Derendorf, H. Pharmacometrics as a discipline is entering the &quot;industrialization&quot; phase: standards, automation, knowledge sharing, and training are critical for future success. J Clin Pharmacol, 50 (9 Suppl), 9S-19S, 2010.
- Vaddady, PK, Lee, RE, Meibohm, B. In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB. Future Med Chem, 2 (8), 1355-69, 2010.
- Kumar, R, Seibold, MA, Aldrich, MC, Williams, LK, Reiner, AP, Colangelo, L, Galanter, J, Gignoux, C, Hu, D, Sen, S, Choudhry, S, Peterson, EL, Rodriguez-Santana, J, Rodriguez-Cintron, W, Nalls, MA, Leak, TS, O'Meara, E, Meibohm, B, Kritchevsky, SB, Li, R, Harris, TB, Nickerson, DA, Fornage, M, Enright, P, Ziv, E, Smith, LJ, Liu, K, Burchard, EG. Genetic ancestry in lung-function predictions. N Engl J Med, 363 (4), 321-30, 2010.
- Mehrotra, N, Freire, AX, Bauer, DC, Harris, TB, Newman, AB, Kritchevsky, SB, Meibohm, B, ,. Predictors of mortality in elderly subjects with obstructive airway disease: the PILE score. Ann Epidemiol, 20 (3), 223-32, 2010.
- Sharma, A, Pibarot, P, Pilote, S, Dumesnil, JG, Arsenault, M, BÃ©langer, PM, Meibohm, B, Hamelin, BA. Toward optimal treatment in women: the effect of sex on metoprolol-diphenhydramine interaction. J Clin Pharmacol, 50 (2), 214-25, 2010.
- Budha, NR, Lee, RB, Hurdle, JG, Lee, RE, Meibohm, B. A simple in vitro PK/PD model system to determine time-kill curves of drugs against Mycobacteria. Tuberculosis (Edinb), 2009.
- LÃ¤er, S, Barrett, JS, Meibohm, B. The in silico child: using simulation to guide pediatric drug development and manage pediatric pharmacotherapy. J Clin Pharmacol, 49 (8), 889-904, 2009.
- Zhang, Y, Mehrotra, N, Budha, NR, Christensen, ML, Meibohm, B. A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume pediatric plasma specimens. Clin Chim Acta, 398 (1-2), 105-12, 2008.
- Zhang, L, Pfister, M, Meibohm, B. Concepts and challenges in quantitative pharmacology and model-based drug development. AAPS J, 10 (4), 552-9, 2008.
- Dirks, NL, Li, S, Huth, B, Hochhaus, G, Yates, CR, Meibohm, B. Transrepression and transactivation potencies of inhaled glucocorticoids. Pharmazie, 63 (12), 893-8, 2008.
- Hurdle, JG, Lee, RB, Budha, NR, Carson, EI, Qi, J, Scherman, MS, Cho, SH, McNeil, MR, Lenaerts, AJ, Franzblau, SG, Meibohm, B, Lee, RE. A microbiological assessment of novel nitrofuranylamides as anti-tuberculosis agents. J Antimicrob Chemother, 62 (5), 1037-45, 2008.
- Mertens-Talcott, SU, Rios, J, Jilma-Stohlawetz, P, Pacheco-Palencia, LA, Meibohm, B, Talcott, ST, Derendorf, H. Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers. J Agric Food Chem, 56 (17), 7796-802, 2008.
- Albers, S, Meibohm, B, Mir, TS, LÃ¤er, S. Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure. Br J Clin Pharmacol, 65 (4), 511-22, 2008.
- Budha, NR, Lee, RE, Meibohm, B. Biopharmaceutics, pharmacokinetics and pharmacodynamics of antituberculosis drugs. Curr Med Chem, 15 (8), 809-25, 2008.
- Dirks, NL, Nolting, A, Kovar, A, Meibohm, B. Population pharmacokinetics of cetuximab in patients with squamous cell carcinoma of the head and neck. J Clin Pharmacol, 48 (3), 267-78, 2008.
- Budha, NR, Mehrotra, N, Tangallapally, R, Rakesh, , Qi, J, Daniels, AJ, Lee, RE, Meibohm, B. Pharmacokinetically-guided lead optimization of nitrofuranylamide anti-tuberculosis agents. AAPS J, 10 (1), 157-65, 2007.
- Tangallapally, RP, Sun, D, Rakesh, , Budha, N, Lee, RE, Lenaerts, AJ, Meibohm, B, Lee, RE. Discovery of novel isoxazolines as anti-tuberculosis agents. Bioorg Med Chem Lett, 17 (23), 6638-42, 2007.
- Chen, ML, Straughn, AB, Sadrieh, N, Meyer, M, Faustino, PJ, Ciavarella, AB, Meibohm, B, Yates, CR, Hussain, AS. A modern view of excipient effects on bioequivalence: case study of sorbitol. Pharm Res, 24 (1), 73-80, 2007.
- Mehrotra, N, Gupta, M, Kovar, A, Meibohm, B. The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int J Impot Res, 19 (3), 253-64, 2006.
- Song, P, Lamba, JK, Zhang, L, Schuetz, E, Shukla, N, Meibohm, B, Yates, CR. G2677T and C3435T genotype and haplotype are associated with hepatic ABCB1 (MDR1) expression. J Clin Pharmacol, 46 (3), 373-9, 2006.
- Meibohm, B, LÃ¤er, S, Panetta, JC, Barrett, JS. Population pharmacokinetic studies in pediatrics: issues in design and analysis. AAPS J, 7 (2), E475-87, 2005.
- LÃ¤er, S, Elshoff, JP, Meibohm, B, Weil, J, Mir, TS, Zhang, W, Hulpke-Wette, M. Development of a safe and effective pediatric dosing regimen for sotalol based on population pharmacokinetics and pharmacodynamics in children with supraventricular tachycardia. J Am Coll Cardiol, 46 (7), 1322-30, 2005.
- Christensen, ML, Meibohm, B, Capparelli, EV, Velasquez-Mieyer, P, Burghen, GA, Tamborlane, WV. Single- and multiple-dose pharmacokinetics of pioglitazone in adolescents with type 2 diabetes. J Clin Pharmacol, 45 (10), 1137-44, 2005.
- Gupta, M, Kovar, A, Meibohm, B. The clinical pharmacokinetics of phosphodiesterase-5 inhibitors for erectile dysfunction. J Clin Pharmacol, 45 (9), 987-1003, 2005.
- Gupta, M, Yates, CR, Meibohm, B. SYBR Green-based real-time PCR allelic discrimination assay for beta2-adrenergic receptor polymorphisms. Anal Biochem, 344 (2), 292-4, 2005.
- Song, P, Meibohm, B, Yates, CR. LC/MS/MS in drug development: targeting the brain. Biotechniques, Suppl, 19-23, 2005.
- Sharma, A, Pibarot, P, Pilote, S, Dumesnil, JG, Arsenault, M, BÃ©langer, PM, Meibohm, B, Hamelin, BA. Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. J Pharmacol Exp Ther, 313 (3), 1172-81, 2005.
- Dirks, NL, Huth, B, Yates, CR, Meibohm, B. Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther, 42 (12), 701-18, 2004.
- Tang, L, Persky, AM, Hochhaus, G, Meibohm, B. Pharmacokinetic aspects of biotechnology products. J Pharm Sci, 93 (9), 2184-204, 2004.
- Gupta, M, Song, P, Yates, CR, Meibohm, B. Real-time PCR-based genotyping assay for CXCR2 polymorphisms. Clin Chim Acta, 341 (1-2), 93-100, 2004.
- Yates, CR, Zhang, W, Song, P, Li, S, Gaber, AO, Kotb, M, Honaker, MR, Alloway, RR, Meibohm, B. The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol, 43 (6), 555-64, 2003.
- Song, P, Li, S, Meibohm, B, Gaber, AO, Honaker, MR, Kotb, M, Yates, CR. Detection of MDR1 single nucleotide polymorphisms C3435T and G2677T using real-time polymerase chain reaction: MDR1 single nucleotide polymorphism genotyping assay. AAPS PharmSci, 4 (4), E29, 2003.
- Meibohm, B, Beierle, I, Derendorf, H. How important are gender differences in pharmacokinetics. Clin Pharmacokinet, 41 (5), 329-42, 2002.
- LÃ¤er, S, Mir, TS, Behn, F, Eiselt, M, Scholz, H, Venzke, A, Meibohm, B, Weil, J. Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters. Am Heart J, 143 (5), 916-22, 2002.
- Meibohm, B, Derendorf, H. Pharmacokinetic/pharmacodynamic studies in drug product development. J Pharm Sci, 91 (1), 18-31, 2002.
- LÃ¤er, S, Meibohm, B, Mir, TS, Hulpke-Wette, M. Termination of automatic atrial tachycardia in an infant by adequate sotalol dosing. Indication of clinically relevant age-dependent pharmacokinetics of sotalol. Eur J Clin Pharmacol, 57 (2), 181-2, 2001.
- Meibohm, B, Zhang, W, Beierle, I, Meyer, MC. Epistaxis associated with elevation of INR in a patient switched to generic warfarin--another view. Pharmacotherapy, 20 (7), 866-9; discussion 869-71, 2000.
- Derendorf, H, Hochhaus, G, Krishnaswami, S, Meibohm, B, MÃ¶llmann, H. Optimized therapeutic ratio of inhaled corticosteroids using retrometabolism. Pharmazie, 55 (3), 223-7, 2000.
- Beierle, I, Meibohm, B, Derendorf, H. Gender differences in pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther, 37 (11), 529-47, 1999.
- Meibohm, B, Derendorf, H, MÃ¶llmann, H, FrÃ¶hlich, P, Tromm, A, Wagner, M, Homrighausen, S, Krieg, M, Hochhaus, G. Mechanism-based PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids. Int J Clin Pharmacol Ther, 37 (8), 367-76, 1999.
- Meibohm, B, Hochhaus, G, MÃ¶llmann, H, Barth, J, Wagner, M, Krieg, M, StÃ¶ckmann, R, Derendorf, H. A pharmacokinetic/pharmacodynamic approach to predict the cumulative cortisol suppression of inhaled corticosteroids. J Pharmacokinet Biopharm, 27 (2), 127-47, 1999.
- Derendorf, H, Meibohm, B. Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives. Pharm Res, 16 (2), 176-85, 1999.
- Derendorf, H, Hochhaus, G, Meibohm, B, MÃ¶llmann, H, Barth, J. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. J Allergy Clin Immunol, 101 (4 Pt 2), S440-6, 1998.
- MÃ¶llmann, H, Wagner, M, Meibohm, B, Hochhaus, G, Barth, J, StÃ¶ckmann, R, Krieg, M, Weisser, H, Falcoz, C, Derendorf, H. Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol, 53 (6), 459-67, 1998.
- MÃ¶llmann, H, Derendorf, H, Barth, J, Meibohm, B, Wagner, M, Krieg, M, Weisser, H, KnÃ¶ller, J, MÃ¶llmann, A, Hochhaus, G. Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation. J Clin Pharmacol, 37 (10), 893-903, 1997.
- Derendorf, H, MÃ¶llmann, H, Hochhaus, G, Meibohm, B, Barth, J. Clinical PK/PD modelling as a tool in drug development of corticosteroids. Int J Clin Pharmacol Ther, 35 (10), 481-8, 1997.
- Meibohm, B, Derendorf, H. Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clin Pharmacol Ther, 35 (10), 401-13, 1997.
- Meibohm, B, Hochhaus, G, Rohatagi, S, MÃ¶llmann, H, Barth, J, Wagner, M, Krieg, M, StÃ¶ckmann, R, Derendorf, H. Dependency of cortisol suppression on the administration time of inhaled corticosteroids. J Clin Pharmacol, 37 (8), 704-10, 1997.
- Rohatagi, S, Bye, A, Falcoz, C, Mackie, AE, Meibohm, B, MÃ¶llmann, H, Derendorf, H. Dynamic modeling of cortisol reduction after inhaled administration of fluticasone propionate. J Clin Pharmacol, 36 (10), 938-41, 1996.