Introduction: Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy. Current 2D or 3D cell models and animal models often fail to provide data that can effectively translate into clinical trials, leading to pregnant women being excluded from drug development considerations and clinical studies. To address this limitation, we explored the utility of in silico simulation modeling and microfluidic-based organ-on-a-chip platforms to assess potential interventional agents.Methods: We developed a multi-organ feto-maternal interface on-chip (FMi-PLA-OOC) utilizing microfluidic channels to maintain intercellular interactions among seven different cell types (fetal membrane-decidua-placenta). This platform enabled the investigation of drug pharmacokinetics in vitro. Pravastatin, a model drug known for its efficacy in reducing oxidative stress and inflammation during pregnancy and currently in clinical trials, was used to test its transfer rate across both feto-maternal interfaces. The data obtained from FMi-PLA-OOC were compared with existing data from in vivo animal models and ex vivo placenta perfusion models. Additionally, we employed mechanistically based simulation software (Gastroplus®) to predict pravastatin pharmacokinetics in pregnant subjects based on validated nonpregnant drug data.Results: Pravastatin transfer across the FMi-PLA-OOC and predicte...

Salvianolic acid A (SAA) is a water-soluble phenolic acid component from Salvia miltiorrhiza Bunge currently under development for myocardial protection treatment for coronary heart disease (CHD). We investigated the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of SAA. Additionally, a physiologically based pharmacokinetic (PBPK) model was developed to simulate the pharmacokinetics of SAA. This was a first-in-human (FIH), randomized, double-blind, placebo-controlled, single, and multiple-dose study in 116 healthy Chinese subjects with the range of 10–300 mg and 60–200 mg SAA, respectively. SAA was well tolerated at all dose levels, following both single and multiple doses, with a low overall incidence of treatment-emergent adverse events (TEAEs) which appeared to be no dose-related. The main pharmacokinetic parameter of SAA, assessed by the power model, was the lack of proportionality with the dose range after single dosing. The 90% CIs of the slope β of Cmax (1.214 [1.150–1.278]) and AUC0-t (1.222 [1.156–1.288]) were not within the predefined acceptance range, and the direction of the deviation was higher than expected. PBPK modeling suggested the transfer ability saturation of hepatic organic anion-transporting polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp) might result in a relatively low distribution rate at higher doses. Clinical plasma concentrations observed were in good agreement with PBPK prediction. SAA showed well-charact...

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Artificial intelligence comes from sophisticated computer model based “machine learning” and “deep learning.” Microsoft and IBM provide AI infrastructure using modeling tools. Farmers are able to develop intelligent planting, irrigating and harvesting systems to increase yields to feed the expanding population of our planet.

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UML-PSI: the UML Performance SImulator Moreno Marzolla Simonetta Balsamo Dipartimento di Informatica Universit̀a Ca’ Foscari di Venezia via Torino 155, 30172 Mestre (VE),…

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Drug bioavailability is a major failing point of new pharmaceuticals i.e. drugs fail to reach their target or fail to stay there long enough for therapeutic effect. Compounding this issue, significant variability exists between patients and how they metabolize and distribute a drug. We present WebPK …

A new pharmacokinetic simulation program called PharmaSim has been developed. It is focused on the simulation of drug plasma levels based on compartment models. The major advantage lies in the easy visualization of curves and the high speed of the simulations. When the value of a parameter changes t …

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AAPS PharmSciTech - The oral drug bioavailability (BA) problems have remained inevitable over the years, impairing drug efficacy and indirectly leading to eventual human morbidity and mortality....

Clinical Pharmacokinetics - When scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in...

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Journal of Computer-Aided Molecular Design - Leishmaniasis is a neglected tropical disease caused by Leishmania parasites and is associated to more than 1.3 million cases annually. Some of the...

Abstract. Background: Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. Summary: The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs – specifically those that contain lipids in their structure, with special reference to IR injury.

s simulation platform. Methods A Windows Presentation Foundation application that emulates an Aespire anesthesia workstation was created. The Gas Man simulator (Med Man Simulations) was used as a reference for the pharmacokinetic model. A concordance analysis was made between the results obtained by our model and the reference, in open and semiclosed circuit, in both 70- and 140-kg patients. Results The mean of the differences between the compartments was less than 0.01 vol% in all circumstances. The percentile rank P2.5 to P97.5 was less than 0.5 vol% in all compartments, except for the open circuit compartment. Conclusions No significant differences were found between both pharmacokinetic models. We consider that our software-based anesthesia workstation can be useful for simulating mechanical ventilation and halogenated administration in different scenarios....