Towards More Robust Evaluation of the Predictive Performance of Physiologically Based Pharmacokinetic Models: Using Confidence Intervals to Support Use of Model-Informed Dosing in Clinical Care
ConclusionsWith this method, we aim to provide a tool to further increase confidence in PBPK model performance and facilitate its use for directly informing drug dosing in clinical care. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - February 15, 2024 Category: Drugs & Pharmacology Source Type: research
Moving Beyond Boundaries: Utilization of Longitudinal Exposure –Response Model for Bounded Outcome Score to Inform Decision Making in the Accelerated Drug Development Paradigm
ConclusionThe CBO modeling approach and simulation supported the single pivotal trial strategy and guided dose selection in the accelerated drug development program of ritlecitinib, which can be applied to many indications where efficacy is measured on a bounded scale. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - February 15, 2024 Category: Drugs & Pharmacology Source Type: research
Lumacaftor/Ivacaftor Population Pharmacokinetics in Pediatric Patients with Cystic Fibrosis: A First Step Toward Personalized Therapy
Conclusions This study is the first analysis of lumacaftor/ivacaftor PPK in children with CF. These data suggest
that dose adjustment is required after identifying variability factors to optimize efficacy. The use of therapeutic drug
monitoring as a basis for dose adjustment in children with CF may be useful. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - February 4, 2024 Category: Drugs & Pharmacology Source Type: research
Salivary Therapeutic Drug Monitoring of Antimicrobial Therapy: Feasible or Futile?
AbstractPersonalised drug dosing through therapeutic drug monitoring (TDM) is important to maximise efficacy and to minimise toxicity. Hurdles preventing broad implementation of TDM in routine care include the need of sophisticated equipment and highly trained staff, high costs and lack of timely results. Salivary TDM is a non-invasive, patient-friendly alternative to blood sampling, which has the potential to overcome barriers with traditional TDM. A mobile UV spectrophotometer may provide a simple solution for analysing drug concentrations in saliva samples. Salivary TDM utilising point-of-care tests can support personal...
Source: Clinical Pharmacokinetics - February 1, 2024 Category: Drugs & Pharmacology Source Type: research
Reporting Coefficient of Variation for Logit, Box-Cox and Other Non-log-normal Parameters
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - February 1, 2024 Category: Drugs & Pharmacology Source Type: research
Salivary Therapeutic Drug Monitoring of Antimicrobial Therapy: Feasible or Futile?
AbstractPersonalised drug dosing through therapeutic drug monitoring (TDM) is important to maximise efficacy and to minimise toxicity. Hurdles preventing broad implementation of TDM in routine care include the need of sophisticated equipment and highly trained staff, high costs and lack of timely results. Salivary TDM is a non-invasive, patient-friendly alternative to blood sampling, which has the potential to overcome barriers with traditional TDM. A mobile UV spectrophotometer may provide a simple solution for analysing drug concentrations in saliva samples. Salivary TDM utilising point-of-care tests can support personal...
Source: Clinical Pharmacokinetics - February 1, 2024 Category: Drugs & Pharmacology Source Type: research
Reporting Coefficient of Variation for Logit, Box-Cox and Other Non-log-normal Parameters
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - February 1, 2024 Category: Drugs & Pharmacology Source Type: research
Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Moderate-to-Severe Psoriasis
AbstractPsoriasis is a common inflammatory immune disorder due to chronic activation of the adaptive and innate immune responses. Therapies for psoriasis target reducing inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-22. Patients with inflammatory disorders have reduced metabolism by cytochrome P450 enzymes in the liver. The pharmacokinetic and pharmacodynamic changes due to psoriasis also have an impact on reaching therapeutic concentrations of the drug. Pharmacokinetic and pharmacodynamic data help determine the safety and clinical considerations necessary when utilizing drugs...
Source: Clinical Pharmacokinetics - January 27, 2024 Category: Drugs & Pharmacology Source Type: research
Maternal Ezetimibe Concentrations Measured in Breast Milk and Its Use in Breastfeeding Infant Exposure Predictions
ConclusionsPBPK model-predicted ezetimibe and EZE-glucuronide exposures and UAR suggest that breastfeeding infants would receive non-therapeutic exposures. Future work should involve a ‘mother-infant pair study’ to ascertain breastfed infant plasma ezetimibe and EZE-glucuronide concentrations to confirm the findings of this work. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - January 26, 2024 Category: Drugs & Pharmacology Source Type: research
Use of Pharmacokinetic and Pharmacodynamic Data to Develop the CDK4/6 Inhibitor Ribociclib for Patients with Advanced Breast Cancer
AbstractRibociclib is an orally bioavailable, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. CDK4/6 inhibition by ribociclib leads to retinoblastoma tumor suppressor protein (Rb) reactivation, thereby restoring Rb-mediated cell cycle arrest. Ribociclib is approved for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2−) advanced breast cancer (ABC), at the dose of 600 mg once daily (QD) during cycles of 21 days on/7 days off, with optional dose reduction to 400 mg and 200 mg. Ribociclib is rapidly absorbed with a median time to reach ...
Source: Clinical Pharmacokinetics - January 20, 2024 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetic/Pharmacodynamic Models for P2Y12 Inhibitors: A Systematic Review and Clinical Appraisal Using Exposure Simulation
ConclusionLowering the maintenance dose of ticagrelor from 90 to 60 mg bid effectively reduces bleeding risk without increasing thrombotic infarction risk in elderly, small-weight Asian females. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - January 20, 2024 Category: Drugs & Pharmacology Source Type: research
Use of Pharmacokinetic and Pharmacodynamic Data to Develop the CDK4/6 Inhibitor Ribociclib for Patients with Advanced Breast Cancer
AbstractRibociclib is an orally bioavailable, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. CDK4/6 inhibition by ribociclib leads to retinoblastoma tumor suppressor protein (Rb) reactivation, thereby restoring Rb-mediated cell cycle arrest. Ribociclib is approved for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2−) advanced breast cancer (ABC), at the dose of 600 mg once daily (QD) during cycles of 21 days on/7 days off, with optional dose reduction to 400 mg and 200 mg. Ribociclib is rapidly absorbed with a median time to reach ...
Source: Clinical Pharmacokinetics - January 20, 2024 Category: Drugs & Pharmacology Source Type: research
