Purpose: Frequent consumption of high-fat meals and prolonged sedentary time are prevalent lifestyles that have been associated with an increased risk of vascular and metabolic complications. This study evaluated the acute effects of interrupting prolonged sitting with stair climbing on vascular and metabolic function after a high-fat meal.
Methods: In a randomized, cross-over trial, 12 healthy adults (age: 23.5 ± 2.9 years) consumed a high-fat meal, followed by either 1) a 4-h uninterrupted sitting (sitting trial) or 2) a 4-h sitting interrupted with a 5-min stair climbing (average intensity: 66% of heart rate reserve) every hour (interrupted trial). Plasma triglyceride and glucose concentrations, as well as popliteal artery blood flow and shear rate were assessed at baseline and every hour after a high-fat meal, whereas brachial artery flow-mediated dilation was assessed at baseline and again at the end of each trial.
Results: Plasma triglyceride and glucose concentrations increased after a high-fat meal and returned to baseline at the end of both trials. Following a high-fat meal, brachial artery flow-mediated dilation decreased in the sitting trial, but not in the interrupted trial (sitting trial: 9.65 ± 2.63% to 7.84 ± 2.36%; interrupted trial: 9.41 ± 2.61% to 10.34 ± 3.30%, p = 0.009 for interaction). Compared with the sitting trial, the interrupted trial improved popliteal blood flow and shear rate (p = 0.004 and p = 0.008 for interaction, respectively).
Conclusions: These findings suggest that interrupting prolonged sitting with stair climbing may be an effective lifestyle strategy to prevent against vascular dysfunction that might occur as a result of prolonged sitting after consuming a high-fat meal in young healthy adults.
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http://dx.doi.org/10.1007/s00421-020-04321-9 | DOI Listing |
Clin Pharmacol Drug Dev
January 2025
Gilead Sciences, Inc., Foster City, CA, USA.
Lenacapavir is a potent, long-acting HIV-1 capsid inhibitor used in combination with other antiretrovirals to treat HIV-1 infection. The pharmacokinetics of orally administered drugs may be affected by food intake or coadministration of acid-reducing agents (ARA). Two Phase 1 studies were conducted on healthy participants to evaluate the effect of food and the impact of the histamine H-receptor antagonist famotidine in parallel cohorts.
View Article and Find Full Text PDFPhysiol Behav
January 2025
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address:
Food cravings increase calorie-dense food intake, contributing to weight gain. Although reductions in food cravings are frequently reported during weight loss, it remains unclear whether these changes are sustained during weight maintenance. The study objective was to investigate associations between food cravings and weight changes in a 12-month weight loss trial followed by 12 months of maintenance.
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January 2025
PTC Therapeutics, Warren, NJ, USA.
Sepiapterin is an exogenously synthesized new chemical entity that is structurally equivalent to endogenous sepiapterin, a biological precursor of tetrahydrobiopterin (BH), which is a cofactor for phenylalanine hydroxylase. Sepiapterin is being developed for the treatment of hyperphenylalaninemia in pediatric and adult patients with phenylketonuria (PKU). This study employed concentration-QT interval analysis to assess QT prolongation risk following sepiapterin treatment.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Pharmacy, National and Kapodistrian University of Athens, Zografou 15771, Greece.
The simulation of antral conditions for estimating drug apparent equilibrium solubility after a high-calorie, high-fat meal is challenging. In this study, (1) we measured the apparent equilibrium solubility of two model lipophilic drugs, ketoconazole and danazol, in antral aspirates collected at various time points after a minced high-calorie, high-fat meal and a glass of water 30 min after initiation of meal administration, and we designated one point estimate for ketoconazole and one point estimate for danazol; (2) we evaluated the usefulness of FeSSGF-V2 and FEDGAS pH = 3 in reproducing the two point estimates; (3) we evaluated potential compositions of FeSSGF-V3 that simulate the pH, the buffer capacity toward both less acidic and more acidic values, and the antral lipid and protein contents with easily accessible, commercially available products, and (4) we identified the most useful composition of FeSSGF-V3 for reproducing the two point estimates. For both model drugs, apparent solubility in FeSSGF-V2 and in FEDGAS pH 3 deviated substantially from the corresponding point estimate.
View Article and Find Full Text PDFAAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
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