A journey into siRNA therapeutics development: A focus on Pharmacokinetics and Pharmacodynamics.

siRNA therapeutics are emerging novel modalities targeting highly specific mRNA via RNA interference mechanism. Its unique pharmacokinetics (PKs) and pharmacodynamics (PDs) are significant challenges for clinical use. Furthermore, naked siRNA is a highly soluble macromolecule with a negative charge, making plasma membrane penetration a significant hurdle.

Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.

Even though several new targets (mostly viral infection) for drug repurposing of pyronaridine and artesunate have recently emerged in vitro and in vivo, inter-species pharmacokinetic (PK) data that can extend nonclinical efficacy to humans has not been reported over 30 years of usage. Since extrapolation of animal PK data to those of humans is essential to predict clinical outcomes for drug repurposing, this study aimed to investigate inter-species PK differences in three animal species (hamster, rat, and dog) and to support clinical translation of a fixed-dose combination of pyronaridine and artesunate. PK parameters (e.

Long-acting injectable donepezil microspheres: Formulation development and evaluation.

Novel formulations of donepezil (DNP)-loaded microspheres based on a bio-degradable polymer of poly(lactic-co-glycolic acid) (PLGA) with a one-month duration of effect were developed, aimed at reducing dosing frequency and adverse effects and improving patient adherence. The spherical and monodispersed DNP-loaded microspheres were precisely fabricated by the Inventage Lab Precision Particle Fabrication method (IVL-PPFM®) based on micro-electromechanical systems (MEMS) and microfluidic technology. The types of polymers and end-groups, the drug/polymer ratio (DPR), and the routes of administration for DNP were studied to ensure an effective concentration and desired duration.

Pharmacokinetic-pharmacodynamic modeling approach for dose prediction of the optimal long-acting injectable formulation of finasteride.

A controlled drug release formulation based on the subcutaneous injection of poly (lactic-co-glycolic acid) (PLGA) microspheres loaded with finasteride was prepared and evaluated for monthly delivery. After selection of biodegradable polymer and polymer-to-finasteride ratio, the formulation was characterized. Scanning electron microscopy (SEM) and laser-light particle size analysis were used to examine the morphology, surface structure, and particle size.

Evaluation of Lidocaine and Metabolite Pharmacokinetics in Hyaluronic Acid Injection.

Lidocaine-incorporated hyaluronic acid injection (LHA) is considered a promising way to increase patient compliance. Various reviews and analyses have been conducted to verify that the addition of lidocaine had no effect on the product quality of hyaluronic acid injections. However, possible pharmacokinetic (PK) alterations of lidocaine and its active metabolites, monoethylglycylxylidide (MEGX) and glycylxylidide (GX), in hyaluronic acid injection have not been studied so far.

Gender differences in pharmacokinetics of perfluoropentanoic acid using non-linear mixed-effect modeling in rats.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been used in various industrial applications for many years. Long-chain PFASs are ubiquitous in wildlife and are reported to have a long elimination half-life in biological systems. Moreover, significant gender difference exists in the elimination of PFASs, where less is eliminated in male than in female.

A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits.

Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet.

Development of Level A In Vitro-Vivo Correlation for Electrosprayed Microspheres Containing Leuprolide: Physicochemical, Pharmacokinetic, and Pharmacodynamic Evaluation.

This study optimized the preparation of electrosprayed microspheres containing leuprolide and developed an in vitro-in vivo correlation (IVIVC) model that enables mutual prediction between in vitro and in vivo dissolution. The pharmacokinetic (PK) and pharmacodynamic (PD) study of leuprolide was carried out in normal rats after subcutaneous administration of electrosprayed microspheres. The parameters of the IVIVC model were estimated by fitting the PK profile of Lucrin depot to the release compartment of the IVIVC model, thus the in vivo dissolution was predicted from the in vitro dissolution.

Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling.

Extrapolation of pharmacokinetic (PK) parameters from in vitro or in vivo animal to human is one of the main tasks in the drug development process. Translational approaches provide evidence for go or no-go decision-making during drug discovery and the development process, and the prediction of human PKs prior to the first-in-human clinical trials. In vitro-in vivo extrapolation and allometric scaling are the choice of method for projection to human situations.

Pharmacokinetic Profile of Kaurenoic Acid after Oral Administration of Araliae Continentalis Radix Extract Powder to Humans.

The objective of this study was to characterize pharmacokinetics (PKs) of kaurenoic acid (KAU) after administration of the clinical usual dose of Araliae Continentalis Radix extract powder to Korean subjects for the first time and evaluate the mechanism of its absorption . A simple, sensitive, and selective analytical method was developed for the detection of KAU in human plasma. Concentrations of KAU were quantified by ultra-performance liquid chromatography tandem mass spectrometry after simple liquid⁻liquid extraction.

Exploring sex differences in human health risk assessment for PFNA and PFDA using a PBPK model.

Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference.

Risk factors for linezolid-induced thrombocytopenia in patients without haemato-oncologic diseases.

This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato-oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.

Pharmacokinetic-Pharmacodynamic Model for the Testosterone-Suppressive Effect of Leuprolide in Normal and Prostate Cancer Rats.

This study developed the pharmacokinetic (PK)-pharmacodynamic (PD) model of the testosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and leuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the routes of administration (intravenous and subcutaneous injection) and kinds of formulation (vehicle, leuprolide solution, and SR depot). The PK profile after subcutaneous injection of leuprolide solution could be well-described by the one-compartment model.