Pharmacokinetic-Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF/FVIII Concentrate.

Background: Hemophilia A patients are treated with factor (F) VIII prophylactically to prevent bleeding. In general, dosage and frequency are based on pharmacokinetic measurements. Ideally, an alternative dose adjustment can be based on the hemostatic potential, measured with a thrombin generation assay (TGA), like the Nijmegen hemostasis assay.

ChatGPT in pharmacometrics? Potential opportunities and limitations.

The potential of using ChatGPT in pharmacometrics was explored in this study, with a focus on developing a population pharmacokinetic (PK) model for standard half-life factor VIII. Our results demonstrated that ChatGPT can be utilized to accurately obtain typical PK parameters from literature, generate a population PK model in R and develop an interactive Shiny application to visualize the results. ChatGPT's language generation capabilities enabled the development of R codes with minimal programming knowledge and helped to identify as well fix errors in the code.

Quantification of the relationship between desmopressin concentration and Von Willebrand factor in Von Willebrand disease type 1: A pharmacodynamic study.

Introduction: Desmopressin can be used to prevent bleeding in von Willebrand disease (VWD), but the relationship between desmopressin and von Willebrand factor activity (VWF:Act) has yet to be quantified.

Aim: To quantify the relationship between desmopressin dose, its plasma concentration and the VWF:Act response in type 1 VWD patients.

Methods: Forty-seven VWD patients (median age 25 years, IQR: 19-37; median body weight 71 kg, IQR: 59-86) received an IV desmopressin dose of .

Is pharmacokinetic-guided dosing of desmopressin and von Willebrand factor-containing concentrates in individuals with von Willebrand disease or low von Willebrand factor reliable and feasible? A protocol for a multicentre, non-randomised, open label cohort trial, the OPTI-CLOT: to WiN study.

Introduction: Von Willebrand disease (VWD) is a bleeding disorder, caused by a deficiency or defect of von Willebrand factor (VWF). In case of medical procedures or bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to increase plasma VWF and factor VIII (FVIII). However, in many cases these factor levels are outside the targeted range.

Impact of enantiomer-specific changes in pharmacokinetics between infants and adults on the target concentration of racemic ketorolac: A pooled analysis.

Aims: Ketorolac is a nonsteroidal anti-inflammatory racemic drug with analgesic effects only attributed to its S-enantiomer. The aim of this study is to quantify enantiomer-specific maturational pharmacokinetics (PK) of ketorolac and investigate if the contribution of both enantiomers to the total ketorolac concentration remains equal between infants and adults or if a change in target racemic concentration should be considered when applied to infants.

Methods: Data were pooled from 5 different studies in adults, children and infants, with 1020 plasma concentrations following single intravenous ketorolac administration.

Optimising the dose of clonidine to achieve sedation in intensive care unit patients with population pharmacokinetics.

Aims: The aim of this study was to investigate the population pharmacokinetics (PK) of clonidine in intensive care unit (ICU) patients in order to develop a dosing regimen for sedation.

Methods: We included 24 adult mechanically ventilated, sedated patients from a mixed medical and surgical ICU. Intravenous clonidine was added to standard sedation in doses of 600, 1200 or 1800 μg/d.