nlme

Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasian populations has been conducted for granisetron patches. This study focused on the ethnic differences in pharmacokinetics (PK) of granisetron transdermal delivery system (GTDS) between Chinese and Caucasians and the influence of demographic covariates on pharmacokinetics (age, weight, height, body mass index, sex)...

OBJECTIVES: Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM)...

BACKGROUND: Ivermectin (IVM) is a broad-spectrum anthelmintic drug used to treat diseases caused by filarial worms, such as onchocerciasis and lymphatic filariasis (LF). IVM is part of a triple-drug therapy used by the Mass Drug Administration (MDA) as a preventive strategy to eradicate LF in sub-Saharan Africa. The drug shows high variability in drug exposure in previous pharmacokinetic studies. This study aims to build a population pharmacokinetic (PopPK) model to identify and quantify the possible sources of the variability of IVM exposure after a single-oral dose in LF-infected subjects and healthy individuals...

Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium have yet to be verified. Hence, we conducted a randomized controlled pilot study to evaluate the efficacy of QTP monotherapy in patients with bipolar depression with mixed features defined by DSM-5 and compared the combination therapy of QTP plus valproate (QTP + V) versus QTP plus lithium (QTP + L) for those patients who responded insufficiently to QTP monotherapy...

BACKGROUND AND OBJECTIVE: Respiratory diseases caused by viruses are a major human health problem. To better control the infection and understand the pathogenesis of these diseases, this paper studied SARS-CoV-2, a novel coronavirus outbreak, as an example. METHODS: Based on coupled computational fluid and particle dynamics (CFPD) and host-cell dynamics (HCD) analyses, we studied the viral dynamics in the mucus layer of the human nasal cavity-nasopharynx. To reproduce the effect of mucociliary movement on the diffusive and convective transport of viruses in the mucus layer, a 3D-shell model was constructed using CT data of the upper respiratory tract (URT) of volunteers...

Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals...

CONTEXT: Intramuscular (IM) testosterone enanthate (TE) and testosterone pellets were US Food and Drug Administration approved before 1962 for pediatric use but not studied in controlled trials in adolescents. OBJECTIVE: An analysis using nonlinear mixed effect (NLME) modeling was designed to evaluate the adult pharmacokinetics (PK) of subcutaneous (SC) and IM TE. This model was used to simulate SC and IM TE administration in adolescents of different weight groups...

BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. METHODS: Patients treated with polymyxin B for CRO pneumonia were enrolled...

Fractional differential equations (FDEs), i.e. differential equations with derivatives of non-integer order, can describe certain experimental datasets more accurately than classic models and have found application in pharmacokinetics (PKs), but wider applicability has been hindered by the lack of appropriate software. In the present work an extension of NONMEM software is introduced, as a FORTRAN subroutine, that allows the definition of nonlinear mixed effects (NLME) models with FDEs. The new subroutine can handle arbitrary user defined linear and nonlinear models with multiple equations, and multiple doses and can be integrated in NONMEM workflows seamlessly, working well with third party packages...

Bamboo crown width (CW) is a reliable index for evaluating growth, yield, health and vitality of bamboo, and light capture ability and carbon fixation efficiency of bamboo forests. Based on statistical results produced from fitting the eight basic growth functions using data from 1374 Phyllostachys pubescens in Yixing, Jiangsu Province, China, this study identified the most suitable function (logistic function) to construct a two-level mixed effects (NLME) CW model with the forest block and sample plot-level effects included as random effects in the model...

The objective of this study was to evaluate blood cells and metabolites, insulin-like growth factor-1 (IGF-1), digestibility, internal organs weight and histology, gene expression, and spleen cell proliferation of pre-weaned bull calves supplemented with a blend of essential oils in milk replacer (MR). Sixteen newborn Holstein × Gyr crossbred dairy bull calves, with body weight at birth of 33.3 ± 3.7 kg, were housed in individual sand bedded pens, blocked by genetic composition, and randomly assigned to 1 of 2 treatments in a randomized complete block design: Control (CON, n = 8) and blend of essential oils supplementation (BEO, n = 8, 1 g/day/calf, Apex Calf, Adisseo, China)...

PURPOSE: Personalized treatment planning in Molecular Radiotherapy (MRT) with accurately determining the absorbed dose is highly desirable. The absorbed dose is calculated based on the Time-Integrated Activity (TIA) and the dose conversion factor. A crucial unresolved issue in MRT dosimetry is which fit function to use for the TIA calculation. A data-driven population-based fitting function selection could help solve this problem. Therefore, this project aims to develop and evaluate a method for accurately determining TIAs in MRT, which performs a Population-Based Model Selection within the framework of the Non-Linear Mixed-Effects (NLME-PBMS) model...

PURPOSE: This project aims to develop and evaluate a method for accurately determining time-integrated activities (TIAs) in single-time-point (STP) dosimetry for molecular radiotherapy. It performs a model selection (MS) within the framework of the nonlinear mixed-effects (NLME) model (MS-NLME). METHODS: Biokinetic data of [111 In]In-DOTATATE activity in kidneys at T1 = (2.9 ± 0.6) h, T2 = (4.6 ± 0...

Background: TQ-B3203 is a novel topoisomerase I inhibitor currently in development for the treatment of advanced solid tumors. Great differences in pharmacokinetic characteristics were found among individuals according to the phase I clinical trial following intravenous administration of TQ-B3203 liposome injection (TLI) in Chinese patients with advanced solid tumors. Thus, it is significant to establish a population pharmacokinetic model to find the key factors and recognize their effect on pharmacokinetic parameters in order to guide individualized administration...

OBJECTIVES: To characterize the pharmacokinetics (PK) of polymyxin B in Chinese critically ill patients. The factors significantly affecting PK parameters are identified, and a limited sampling strategy for therapeutic drug monitoring of polymyxin B is explored. METHODS: Thirty patients (212 samples) were included in a population PK analysis. A limited sampling strategy was developed using Bayesian estimation, multiple linear regression and modified integral equations...

This work is on the design, fabrication and characterization of a hexagonal ferrite band-pass filter that can be tuned either with a magnetic field or an electric field. The filter operation is based on a straight-edge Y-type hexagonal ferrite resonator symmetrically coupled to the input and output microstrip transmission lines. The Zn2 Yfilter demonstrated magnetic field tunability in the 8-12 GHz frequency range by applying an in-plane bias magnetic field H0 provided by a built-in permanent magnet. The insertion loss and 3 dB bandwidth within this band were 8...

BACKGROUND: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration-time curve (AUC0-12 ) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are reported for them...

Ponazuril is a triazine anticoccidial drug which is the main metabolite of toltrazuril in animals, it has excellent activity against many protozoa, including Cystoisospora suis , and has broad application prospects in the control of swine coccidiosis. To evaluate the pharmacokinetic and excretion characteristics of ponazuril, 12 healthy piglets aged 10-14 days were divided into 2 groups for pharmacokinetic studies, which were given 20 mg/kg body weight ponazuril orally and intravenously, respectively. And 6 other piglets were housed individually in metabolic cages and given the same oral dose of ponazuril...

BACKGROUND: Linezolid is a valuable therapeutic option for infections of the central nervous system caused by multi-drug resistant Gram-positive pathogens. Data regarding linezolid pharmacokinetics in cerebrospinal fluid from post-operative neurosurgical patients have revealed wide inter-individual variability. The objectives of this study were to establish a population pharmacokinetic model for linezolid in plasma and cerebrospinal fluid, as well as to optimize dosing strategies in this susceptible population...

INTRODUCTION: Vancomycin is used in proven or suspected MRSA and MRE infections. An AUC/MIC ratio of ≥400 is the current accepted critical PK/PD"efficacy" target of vancomycin activity. The present study was conducted to ascertain the appropriateness of practice of current dosage regimen of vancomycin (1 g BD) based on population pharmacokinetic approach. METHODS: A single-center prospective study with the ICU setting of a tertiary care center was conducted...