Population pharmacokinetics of apixaban in a real‐life hospitalized population from the OptimAT study

Gaspar, Frédéric; Terrier, Jean; Favre, Samantha; Gosselin, Pauline; Fontana, Pierre; Daali, Youssef; Lenoir, Camille; Samer, Caroline Flora; Rollason, Victoria; Reny, Jean‐Luc; Csajka, Chantal; Guidi, Monia

doi:10.1002/psp4.13032

Cited by 3 publications

(2 citation statements)

References 44 publications

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“…This implies that IOV essentially functions as IIV. Nevertheless, in specific scenarios, such as when there are only a few instances per individual, it becomes inappropriate to estimate both IOV and IIV, leading to the retention of only IOV, as published earlier [41]. The implementation of IOV varies in other population pharmacokinetics software, making the estimation of IOV without IIV practically impossible.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2024

Animals

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The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low doses. The secondary aims were to identify associated behavioural effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, an intravenous bolus of 1 mg/kg was administered over 2 min. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 min, followed by an infusion at 0.01 mg/kg/min for 1 h. Blood samples were collected for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. Levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady-state racemic ketamine plasma concentration of 150 ng/mL was 0.028 mg/kg/min. Higher scores for behavioural effects were observed within the first five minutes following bolus administration. The most common behaviours observed were disorientation, head movements and staring eyes. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

show abstract

Section: Discussionmentioning

confidence: 99%

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2024

Animals

View full text Add to dashboard Cite

show abstract

“…This implies that IOV essentially functions as IIV. Nevertheless, in specific scenarios, such as when there are only a few instances per individual, it becomes inappropriate to estimate both IOV and IIV, leading to the retention of only IOV as published earlier [41]. The implementation of IOV varies in other population pharmacokinetics software, making the estimation of IOV without IIV practically not possible.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Pharmacokinetics of Ketamine Administered at Low Dose in Awake Dogs

Pargätzi,

Bergadano,

Spadavecchia

et al. 2023

Preprint

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The present study aimed to examine the stereoselective pharmacokinetics of racemic ketamine in dogs at low dose. Secondary aims were to identify associated behavioural side effects and propose a ketamine infusion rate. The study was conducted on nine intact male beagles, with each dog undergoing two treatments (BOL and INF). For treatment BOL, a single intravenous bolus of 1 mg/kg racemic ketamine was administered over 2 minutes. The treatment INF involved an initial bolus of 0.5 mg/kg given over 1 minute, followed by an infusion at 0.01 mg/kg/min for 1 hour. Blood samples were collected from the left cephalic vein for pharmacokinetic analysis. The median R/S enantiomer ratio of ketamine remained close to 1 throughout the study. However, levels of S-norketamine were significantly higher than those of R-norketamine across all time points. Based on the collected data, the infusion rate predicted to achieve a steady state racemic ketamine plasma concentration of 150 ng/mL was 1.7 mg/kg/h. Furthermore, employing ROC curve analysis, a racemic ketamine plasma concentration of 102 ng/mL was defined as the cut-off value, correlating with the occurrence of undesirable behavioural patterns.

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Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis

Gigante,

Tamargo,

Agewall

et al. 2024

European Heart Journal - Cardiovascular Pharmacotherapy

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Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity, who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, and altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimizing antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.

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Population pharmacokinetics of apixaban in a real‐life hospitalized population from the OptimAT study

Cited by 3 publications

References 44 publications

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Stereoselective Pharmacokinetics of Ketamine Administered at a Low Dose in Awake Dogs

Stereoselective Pharmacokinetics of Ketamine Administered at Low Dose in Awake Dogs

Update on antithrombotic therapy and body mass: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and the European Society of Cardiology Working Group on Thrombosis

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