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Abstract There have been numerous investigations of aberrant eating and substance abuse among patients who have undergone bariatric surgery, which affects the metabolism and the pharmacokinetics of alcohol. However, there is a dearth of literature considering the complex interplay between changes in post‐surgery food and alcohol consumption. Furthermore, despite the increasing recognition of issues surrounding replacing food consumption with alcohol consumption (Food and Alcohol Disturbance [FAD]), most emerging research has focused on young adult populations. This perspective reviews and synthesizes the small but growing body of research on the interplay between food and alcohol consumption, particularly FAD, and considers its application to bariatric surgery in general. There are unique considerations for patients who have undergone bariatric surgery. Patients experience altered gastric anatomy, which affects food and alcohol metabolism, and are advised to abstain from drinking alcohol after surgery. After reviewing the available literature, this perspective highlights future directions for research and practice in bariatric surgery.

The emerging discipline of Quantitative Systems Pharmacology (QSP) enables the integration of quantitative experimental data describing the interactions between the various biological processes within the system using mathematical modeling to gain better insights into the factors that drive disease pathogenicity and influence antibiotic pharmacokinetics (PKs)/pharmacodynamics (PDs). Through our perspective we consider the evolution from PK/PD models to mechanism-based and systems-based models and then finally QSP. We further emphasize the need to invest in ambitious research that takes into consideration: (i) the antibiotic PK/PD activity, (ii) the time course of the host immune response to understand the progression of the infection, (iii) and a growing appreciation of the cellular and molecular networks using multi-omics analysis to understand the modulation of antimicrobial therapy at a true systems level., (© 2021 The Authors Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine involved in asthma pathogenesis. In the phase 2b PATHWAY study (ClinicalTrials.gov identifier: NCT02054130), tezepelumab significantly reduced exacerbations in adults with severe, uncontrolled asthma. We used pharmacokinetic (PK) and pharmacodynamic (PD) modeling to guide tezepelumab dose selection for phase 3 trials in patients with severe asthma. PK data from 7 clinical studies were used to develop a population PK model. Population PK-PD models were developed to characterize the relationship between tezepelumab PK and asthma exacerbation rate (AER) and fractional exhaled nitric oxide (FeNO) levels (using phase 2b PD data only). Tezepelumab PK were well described by a 2-compartment model with first-order absorption; PK parameter estimates were consistent with those of other immunoglobulin G2 antibodies. PK-PD models predicted that subcutaneous dosing at 210 mg every 4 weeks was associated with ≈90% of the maximum drug effect of tezepelumab on AER and FeNO; further dose increases were not expected to result in additional, clinically meaningful treatment benefit. No clinically significant covariates of treatment effects on AER and FeNO were identified. Population PK simulations, exposure-response relationships and safety profiles of tezepelumab at doses up to 280 mg every 2 weeks suggested that no dose adjustment based on body weight or for adolescents was required. These results support the selection of 210 mg every 4 weeks subcutaneously as the dose for phase 3 studies of tezepelumab in adults and adolescents with severe asthma., (© 2020, The American College of Clinical Pharmacology.)