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Examining the Impact of Diet-and-Exercise-Induced Weight Loss on Drug Metabolism and Gastric Emptying in Patients with Obesity.
J Clin Pharmacol
January 2025
Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.
Obesity significantly influences drug pharmacokinetics (PK), which challenges optimal dosing. This study examines the effects of diet-and-exercise-induced weight loss on key drug-metabolizing enzymes and gastric emptying in patients with obesity, who frequently require medications for comorbidities. Participants followed a structured weight management program promoting weight loss over 3-6 months and were not concomitantly on potential CYP inducers or inhibitors.
View Article and Find Full Text PDFImpact of Food Physical Properties on Oral Drug Absorption: A Comprehensive Review.
Drug Des Devel Ther
January 2025
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Food-Drug Interaction (FDI) refers to the phenomenon where food affects the pharmacokinetic or pharmacodynamic characteristics of a drug, significantly altering the drug's absorption rate or absorption extent. These Interactions are considered as a primary determinant in influencing the bioavailability of orally administered drugs within the gastrointestinal tract. The impact of food on drug absorption is complex and multifaceted, potentially involving alterations in gastrointestinal physiology, increases in splanchnic blood flow rates, and shifts in the gut microbiota's composition.
View Article and Find Full Text PDFQuantification and prediction of human fetal (-)-Δ-tetrahydrocannabinol/(±)-11-OH-Δ-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity.
Nat Commun
January 2025
Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, WA, USA.
Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3.
View Article and Find Full Text PDFPhysiologically Based Pharmacokinetic Modeling to Refine Dosing of Posaconazole in Young Children.
Clin Ther
January 2025
University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
Purpose: Posaconazole is a broad-spectrum antifungal for treating and preventing invasive fungal infections (IFIs) in immunocompromised individuals, including children as young as 2 years. Available in delayed-release (DR) oral suspension, intravenous formulation, and older immediate-release (IR) formulation (off-label in younger children), dosing harmonization across age groups and formulations remains inconsistent. This inconsistency arises from the unique physiology of young children and posaconazole's pH-dependent absorption.
View Article and Find Full Text PDFA physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.
J Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
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