About

Paul Beringer, PharmD, is a professor in the Titus Family Department of Clinical Pharmacy at the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences. He received his PharmD degree from USC Mann and completed a pharmacy practice residency and a specialty residency in pharmacokinetics at the University of California at San Francisco. His clinical expertise is in cystic fibrosis pharmacotherapy, and he has authored numerous journal articles and book chapters in pharmacokinetics and cystic fibrosis. Beringer has served as chair of the Titus Family Department of Clinical Pharmacy at USC Mann from 2017 to 2022. Currently, he is also an associate professor of clinical medicine with the Department of Pulmonary and Critical Care Medicine at the Keck School of Medicine of USC. His research focuses on pharmacokinetics, pharmacodynamics, and immunomodulatory therapies related to cystic fibrosis and lung injury, including the development and evaluation of antimicrobial peptides and treatment strategies for pulmonary infections and inflammation.

Research topics

• Internal medicine
• Pharmacology
• Medicine
• Intensive care medicine
• Immunology

Selected publications

• Current State of Clinical Care of People With Cystic Fibrosis

  Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · 2026-03-15

  article

  The advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has dramatically changed the landscape of the clinical care of people with cystic fibrosis (PwCF). In particular, highly effective modulator therapy (HEMT) availability for the majority of PwCF has led to changes in pharmacotherapy regimens and clinical outcomes but has also been associated with adverse effects and drug interactions. The role of CFTR modulator therapy perinatally continues to be of great interest, related to both the mother with CF as well as the infant in utero and after birth. As the median life expectancy for PwCF continues to increase, consideration must also be given for treatment of cardiovascular disease and other comorbidities as well as cancer screening and other preventative care measures.

  PublisherDOI

• Predicting Maternal and Fetal Exposures of Elexacaftor–Tezacaftor–Ivacaftor during Pregnancy through Physiologically Based Pharmacokinetic Models

  Clinical Pharmacology & Therapeutics · 2025-05-05 · 7 citations

  articleOpen accessSenior authorCorresponding

  The use of elexacaftor/tezacaftor/ivacaftor (ETI) has been associated with increased fertility in women with cystic fibrosis (CF) and is increasingly used during pregnancy to support both maternal and fetal health. However, little is known about the pharmacokinetics (PK) of ETI during pregnancy, which is crucial for optimizing its efficacy and safety. This study aimed to predict the PK of ETI during pregnancy and to determine the maternal dose required to achieve therapeutic concentrations in both the maternal and fetus. The pregnancy physiological-based pharmacokinetic (PBPK) model within the Simcyp Simulator was used to predict the maternal and feto-placental exposure of ETI. Placental kinetics were parameterized using permeability parameters determined from the physicochemical properties of these compounds. The model closely predicted the observed data, with the observed ETI maternal plasma concentrations, cord concentrations, and infant plasma concentrations mostly falling within the range of predicted 5th to 95th percentiles. Steady-state simulations up to gestational week 40 predicted a continuous decline in ETI concentrations, with the AUC declining to 32.4-37.5% of baseline levels by week 40. However, the 5th percentile of trough concentrations for ETI consistently remained above the efficacy thresholds, both in mother and fetus. Therefore, it appears reasonable to maintain standard dosing regimen during pregnancy, complemented by careful monitoring. A clinical trial, such as the ongoing Maternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS) study, is required to further confirm the efficacy and safety of ETI in this population.

  PublisherOA PDFDOI

• 460 Dose optimization of omadacycline for the treatment of NTM pulmonary disease using a PBPK modeling approach

  Journal of Cystic Fibrosis · 2025-10-01

  articleSenior author
  PublisherDOI

• In Vitro Activity of Imipenem/Relebactam Alone and in Combination Against Cystic Fibrosis Isolates of Mycobacterium abscessus

  Antibiotics · 2025-05-10 · 1 citations

  articleOpen accessSenior authorCorresponding

  Background: Mycobacterium abscessus (MABS) is an opportunistic pathogen that causes chronic, difficult-to-treat pulmonary infections, particularly in people with cystic fibrosis (PwCF), leading to rapid lung function decline and increased morbidity and mortality. Treatment is particularly challenging due to the pathogen’s resistance mechanisms and the need for prolonged multidrug therapy, which is characterized by poor clinical outcomes and highlights the urgent need for novel therapeutic strategies. Imipenem/relebactam, a novel β-lactam-β-lactamase inhibitor combination, demonstrates in vitro activity against resistant MABS strains and effective pulmonary penetration. Prior research indicates synergistic activity of imipenem with various antibiotics against M. abscessus. Objectives: This study aims to evaluate the in vitro activity of imipenem/relebactam, alone and in combination with various antibiotics, against MABS clinical isolates from PwCF (n = 28). Methods: Susceptibility and synergy were assessed using broth microdilution and checkerboard assays. Extracellular time-kill assays were performed to evaluate the bactericidal activity of synergistic three-drug combinations containing imipenem/relebactam. Results: Imipenem/relebactam demonstrated potent in vitro activity against clinical MABS isolates, exhibiting substantial synergy with cefuroxime, cefdinir, amoxicillin, and cefoxitin. Rifabutin, azithromycin, moxifloxacin, clofazimine, and minocycline also demonstrated additive effects with imipenem/relebactam. Extracellular time-kill assays identified imipenem/relebactam + cefoxitin + rifabutin and imipenem/relebactam + cefoxitin + moxifloxacin as the most effective combinations. Conclusions: These findings suggest that imipenem/relebactam may offer a significant advancement in the management of MABS infections in PwCF. The promising efficacy of multidrug regimens combining imipenem/relebactam with agents like cefoxitin, azithromycin, moxifloxacin, clofazimine, and rifabutin highlights potential therapeutic strategies.

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• Quantitative Systems Toxicology Predicts Ivacaftor‐Induced Oxidative Stress Contributes to <scp>CFTR</scp> Modulator Hepatotoxicity

  Clinical Pharmacology & Therapeutics · 2025-09-23 · 2 citations

  articleOpen accessSenior authorCorresponding

  Cystic fibrosis (CF) is a chronic hereditary disease that affects tens of thousands of people worldwide. The introduction of CFTR modulator therapies such as elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved the quality of life of people with CF. However, ETI has been shown in clinical trials to cause elevations in liver enzymes, and real-world cases of drug-induced liver injury (DILI) have also been reported. The mechanism of ETI-mediated DILI is currently unknown, hindering the development of more effective mitigation strategies for this adverse reaction. Through in vitro assays and quantitative systems toxicology modeling using DILIsym, this study revealed that ivacaftor contributed most significantly to ETI-mediated DILI, primarily via reactive oxygen species production, resulting in mitochondrial dysfunction due to electron transport chain inhibition. DILIsym modeling also predicted liver enzyme elevations following daily dosing of ETI at a comparable frequency (6.0%) to that of clinical data (8.0%). Simulations of the therapeutic effects of DILI mitigation strategies for ETI showed that dose reduction and antioxidant administration may significantly reduce the frequency of liver enzyme elevations due to ETI.

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• Evaluation of the drug interaction between rifabutin and elexacaftor/tezacaftor/ivacaftor (ETI)

  Journal of Cystic Fibrosis · 2025-09-17 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Evaluation of Elexacaftor/Tezacaftor/Ivacaftor‐Mediated Drug‐Induced Liver Injury Using a Liver‐On‐Chip Model

  Clinical and Translational Science · 2025-11-01

  articleOpen accessSenior authorCorresponding

  Elexacaftor/tezacaftor/ivacaftor (ETI), a cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy, has provided great improvements in lung function and well-being for people with CF. The use of ETI has been complicated by reports of rare but significant liver function test elevations in clinical trials and drug-induced liver injury (DILI) in real-world use. Previous research by our group revealed that oxidative stress is the major driver of ETI-mediated DILI, and in silico ETI DILI simulations resulted in elevations of the emerging biomarker glutamine dehydrogenase (GLDH) which match the time course of predicted transaminase elevations. The assessment of emerging biomarkers and therapeutic strategies in a clinically relevant model will spur the development of more effective treatments for ETI-mediated DILI. This study used the human-relevant liver-on-chip model to investigate GLDH as a biomarker and ETI dose reduction and silymarin antioxidant administration as therapeutic strategies for ETI-mediated DILI. We found that GLDH was not as sensitive as ALT and albumin for detecting DILI due to ETI. Dose reduction was a more effective treatment strategy for ETI DILI than silymarin, which did not significantly lower ALT levels.

  PublisherOA PDFDOI

• Dose optimization of omadacycline for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD) using a physiologically based pharmacokinetic modeling approach

  Journal of Pharmaceutical Investigation · 2025-10-13

  article
  PublisherDOI

• Challenges and Opportunities for Pharmacogenomics in the Care of People With Cystic Fibrosis

  Pediatric Pulmonology · 2025-10-01

  letter

  Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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• Evaluation of Complex Drug Interactions Between Elexacaftor-Tezacaftor-Ivacaftor and Statins Using Physiologically Based Pharmacokinetic Modeling

  Pharmaceutics · 2025-03-01 · 3 citations

  articleOpen accessSenior authorCorresponding

  Background/Objectives: The increasing use of statins in people with cystic fibrosis (CF) necessitates the investigation of potential drug–drug interactions (DDI) of statins with cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor, tezacaftor, and ivacaftor (ETI). The interactions may involve the potential inhibition of cytochrome P450 isoenzymes (CYPs), organic anion-transporting polypeptides (OATPs), and Breast Cancer Resistance Protein (BCRP) by ETI. This presents a therapeutic challenge in CF due to the potential for elevated statin levels, consequently heightening the risk of myopathy. This study aimed to predict potential DDIs between statins and ETI using a physiologically based pharmacokinetic (PBPK) modeling approach. Methods: We performed in vitro assays to measure the inhibitory potency of ETI against OATPs and CYP2C9 and incorporated these data into our PBPK models alongside published inhibitory parameters for BCRP and CYP3A4. Results: The PBPK simulation showed that atorvastatin had the highest predicted AUC ratio (3.27), followed by pravastatin (2.27), pitavastatin (2.24), and rosuvastatin (1.83). Conclusions: Based on these findings, rosuvastatin appears to exhibit a weak interaction with ETI, whereas other statins exhibited a moderate interaction, potentially requiring appropriate dose reductions. These data indicate potential clinically significant DDIs between ETI and certain statins, which warrants a clinical study to validate these findings.

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Recent grants

• NIH Grant M01RR000043

  NIH · $33.2M · 2010

Frequent coauthors

• Annie Wong‐Beringer

  20 shared

• Adupa P. Rao

  University of Southern California

  19 shared

• Stan G. Louie

  University of Southern California

  16 shared

• Eunjin Hong

  CHA University

  14 shared

• Maria I. Rudis

  Mayo Clinic

  12 shared

• Mark A. Gill

  Durham University

  12 shared

• Peter S. Chung

  University of Southern California

  12 shared

• Timothy J. Bensman

  Center for Drug Evaluation and Research

  10 shared