Clinical and Pre-Clinical Pharmacokinetics and Pharmacodynamics of Bentracimab
AbstractAntiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5 –15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associat...
Source: Clinical Pharmacokinetics - April 28, 2023 Category: Drugs & Pharmacology Source Type: research
Negative Impact of ST-Segment Elevation Myocardial Infarction and Morphine Dose on Ticagrelor Uptake and Pharmacodynamics: A Population PK/PD Analysis of Pooled Individual Participant Data
ConclusionThe developed population PK/PD model confirmed the negative impact of morphine administration and presence of STEMI on ticagrelor PK and antiplatelet effect. Increasing ticagrelor doses seems effective in morphine users without STEMI, whereas the STEMI effect is not entirely reversible.Graphical Abstract (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetics and Probability of Target Attainment Analysis of Nadroparin in Different Stages of COVID-19
ConclusionsDifferent nadroparin dosing is required for patients undergoing mechanical ventilation and extracorporeal membrane oxygenation to achieve the same targets as those for non-critically ill patients.Clinical Trial RegistrationClinicalTrials.gov identifier no. NCT05621915. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
Negative Impact of ST-Segment Elevation Myocardial Infarction and Morphine Dose on Ticagrelor Uptake and Pharmacodynamics: A Population PK/PD Analysis of Pooled Individual Participant Data
ConclusionThe developed population PK/PD model confirmed the negative impact of morphine administration and presence of STEMI on ticagrelor PK and antiplatelet effect. Increasing ticagrelor doses seems effective in morphine users without STEMI, whereas the STEMI effect is not entirely reversible.Graphical Abstract (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetics and Probability of Target Attainment Analysis of Nadroparin in Different Stages of COVID-19
ConclusionsDifferent nadroparin dosing is required for patients undergoing mechanical ventilation and extracorporeal membrane oxygenation to achieve the same targets as those for non-critically ill patients.Clinical Trial RegistrationClinicalTrials.gov identifier no. NCT05621915. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 25, 2023 Category: Drugs & Pharmacology Source Type: research
Integrated Use of In Vitro and In Vivo Information for Comprehensive Prediction of Drug Interactions Due to Inhibition of Multiple CYP Isoenzymes
ConclusionThis framework would be a powerful tool for the reasonable management of various DIs based on all available in vitro and in vivo information. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 19, 2023 Category: Drugs & Pharmacology Source Type: research
Mechanistic Pharmacokinetic/Pharmacodynamic Modeling in Support of a Patient-Convenient, Longer Dosing Interval for Carfilzomib, a Covalent Inhibitor of the Proteasome
ConclusionThis work provides a framework for which mechanistic PK/PD modeling can be used to guide optimization of dosing intervals for therapeutics with significantly longer PD effects than PK, and help further justify patient-convenient, longer dosing intervals. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 18, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma
ConclusionsAccounting for the CD38 turnover and its binding capacity to daratumumab, the QSS approximation provided a mechanistic interpretation of daratumumab PK parameters and consequently well described the concentration- and CD38 dynamics-dependency of daratumumab pharmacokinetics.Clinical studies included in the analysis were registered with the NCT number below athttp://www.ClinicalTrials.govMMY1002 (ClinicalTrials.gov: NCT02116569), MMY1003 (NCT02852837), MMY1004 (NCT02519452), MMY1008 (NCT03242889), GEN501 (NCT00574288), MMY2002 (NCT01985126), MMY3012 (NCT03277105). (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 6, 2023 Category: Drugs & Pharmacology Source Type: research
Vancomycin Clearance in Obese Adults is not Predictive of Clearance in Obese Adolescents
ConclusionThere are apparent differences in vancomycin CL in overweight and obese adults versus overweight and obese adolescents, implying that dosing of vancomycin cannot be directly extrapolated between these populations. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 5, 2023 Category: Drugs & Pharmacology Source Type: research
External Evaluation of Population Pharmacokinetic Models for Precision Dosing: Current State and Knowledge Gaps
AbstractPredicting drug exposures using population pharmacokinetic models through Bayesian forecasting software can improve individual pharmacokinetic/pharmacodynamic target attainment. However, selecting the most adapted model to be used is challenging due to the lack of guidance on how to design and interpret external evaluation studies. The confusion around the choice of statistical metrics and acceptability criteria emphasises the need for further research to fill this methodological gap as there is an urgent need for the development of standards and guidelines for external evaluation studies. Herein we discuss the sci...
Source: Clinical Pharmacokinetics - April 1, 2023 Category: Drugs & Pharmacology Source Type: research
