Track topics on Twitter Track topics that are important to you
We previously verified a physiologically-based pharmacokinetic (PBPK) model for mirabegron in healthy subjects using the Simcyp Simulator by incorporating data on the inhibitory effect on cytochrome P450 (CYP) 2D6 and multi-elimination pathway mediated by CYP3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE). The aim of this study was to use this PBPK model to assess the magnitude of drug-drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta-analyses of literature data suggested that the UGT2B7 abundance and BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the CYP3A4 abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration-time profile for mirabegron in an sRI population (simulated area under the plasma concentration-time curve (AUC) was within 1.5-times that of observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a CYP3A4 inhibitor) was 4.12-times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a CYP2D6 substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.
This article was published in the following journal.
Name: Biopharmaceutics & drug disposition
This work scaled up a previously developed physiologically-based pharmacokinetic (PBPK) model to predict the effects of anti-FcRn agents on the disposition of endogenous IgG in human subjects. Simulat...
Florfenicol (FF) is used in cattle to treat respiratory diseases but could result in tissue residues. This study aimed to develop a population physiologically based pharmacokinetic (PBPK) model to pre...
A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinic...
Use of Physiologically Based Pharmacokinetic Modeling to Identify Physiological and Molecular Characteristics Driving Variability in Axitinib Exposure: A Fresh Approach to Precision Dosing in Oncology.
Axitinib is a second-generation small-molecule vascular endothelial growth factor receptor inhibitor. An axitinib steady-state area under the plasma concentration-time curve (AUC ) >300 ng/mL/hr is as...
The present study assesses the pharmacokinetic profile of Ivermectin (IVM) in healthy human volunteers and aims to create a physiologically-based pharmacokinetic model. Planned indication ...
The purpose of this study is to assess the pharmacokinetics of three doses of oral mirabegron formulations with three different release rates versus three doses of mirabegron administered ...
The objective of the study is to assess the PK, safety and tolerability of a single dose of mirabegron alone and in combination with repeat doses of rifampin, a potent CYP3A4 inducer.
This study evaluates whether a medication called mirabegron is better than placebo (sugar pill) in helping patients with achalasia swallow better. Each patient will receive either mirabegr...
Recent phase III trials have confirmed the efficacy and safety of mirabegron in the treatment of OAB in Europeans, Australians, North Americans, Japanese and Asians. Whether mirabegron 25m...
The prediction or projection of the nature of future problems or existing conditions based upon the extrapolation or interpretation of existing scientific data or by the application of scientific methodology.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.
Predicting the time of OVULATION can be achieved by measuring the preovulatory elevation of ESTRADIOL; LUTEINIZING HORMONE or other hormones in BLOOD or URINE. Accuracy of ovulation prediction depends on the completeness of the hormone profiles, and the ability to determine the preovulatory LH peak.
Laboratory tests demonstrating the presence of physiologically significant substances in the blood, urine, tissue, and body fluids with application to the diagnosis or therapy of disease.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...