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This article discusses the need for improved labeling recommendations for medications used during pregnancy and breastfeeding. Currently, there is a lack of data on the safety and efficacy of drugs for these populations, as they are often excluded from drug development programs. The article highlights the value of Model Informed Drug Development (MIDD) in generating data and improving accessibility to safe and effective medicines. Regulatory developments and advancements in nonclinical drug development methodologies and MIDD are expected to enhance the safe use of medicines during pregnancy and breastfeeding. However, challenges remain, including limited experience with MIDD in this context and the uncertainty associated with model predictions. Efforts are being made to improve knowledge through data collection and the development of new methods. European regulators are open to discussions to improve labeling for medicines used during pregnancy and breastfeeding. [Extracted from the article]

Background: The adverse haemodynamic effects of the intravenous anaesthetic propofol are well known, yet few empirical models have explored the dose-response relationship. Evidence suggests that hypotension during general anaesthesia is associated with postoperative mortality. We developed a mechanism-based model that quantitatively characterises the magnitude of propofol-induced haemodynamic effects during general anaesthesia.Methods: Mean arterial pressure (MAP), heart rate (HR) and pulse pressure (PP) measurements were available from 36 healthy volunteers who received propofol in a step-up and step-down fashion by target-controlled infusion using the Schnider pharmacokinetic model. A mechanistic pharmacodynamic model was explored based on the Snelder model. To benchmark the performance of this model, we developed empirical models for MAP, HR, and PP.Results: The mechanistic model consisted of three turnover equations representing total peripheral resistance (TPR), stroke volume (SV), and HR. Propofol-induced changes were implemented by Emax models on the zero-order production rates of the turnover equations for TPR and SV. The estimated 50% effective concentrations for propofol-induced changes in TPR and SV were 2.96 and 0.34 μg ml-1, respectively. The goodness-of-fit for the mechanism-based model was indistinguishable from the empirical models. Simulations showed that predictions from the mechanism-based model were similar to previously published MAP and HR observations.Conclusions: We developed a mechanism-based pharmacodynamic model for propofol-induced changes in MAP, TPR, SV, and HR as a potential approach for predicting haemodynamic alterations.Clinical Trial Registration: NCT02043938. [ABSTRACT FROM AUTHOR]