res clearance in humans
Allometric Pharmacokinetic Scaling: Towards the Prediction of Human ...
Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds …
Clearance Properties of Nano-sized Particles and Molecules as …
Quantum dots > 8 nm (HD = 8.65 nm) did not demonstrate renal filtration but instead exhibited uptake in the reticuloendothelial system (RES) and lung . The relationship between HD, renal clearance, and total body retention was determined to be sigmoidal with the 50% point for total body clearance at 4 h achieved with an HD of 5.5 nm . Results ...
Renal clearance of perfluorooctane sulfonate and ...
The renal clearances were 10(-5)-fold smaller than the glomerular filtration rate in humans, suggesting the absence of active excretion in human kidneys. The renal clearances of PFOA and PFOS were approximately one-fifth of the total clearance based on their serum half-lives, assuming a one-compartment model.
Limitations of the hCMEC/D3 cell line as a model for Aβ clearance …
The hCMEC/D3 cell line has been characterized as a valid model for the BBB. In this study we evaluated the use of this model to study Aβ clearance across the BBB, with an emphasis on brain-to-blood directional permeability. Barrier integrity of hCMEC/D3 monolayers was confirmed for large molecules in both the apical to basolateral and the ...
Mechanisms tagging senescent red blood cells for clearance in …
This review focuses on the analysis and evaluation of the diverse senescence markers suggested to prime red blood cells (RBC) for clearance in humans. These tags develop in the course of biochemical and structural alterations accompanying RBC aging, as the decrease of activities of multiple enzymes, the gradual accumulation of …
Determinants of Acquisition and Clearance of Human …
Best Pract Res Clin Obstet Gynaecol 2018; 47:2–13. ... McDuffie K, et al. Prevalence, acquisition, and clearance of cervical human papillomavirus infection among women with normal cytology: Hawaii human papillomavirus cohort study. Cancer Res 2008; 68:8813–8824. [PMC free article] [Google Scholar]
Prediction of Human Drug Clearance from Two Species: A …
The empirical and physiological predictive approaches to human clearance were evaluated using preclinical in vitro and in vivo data of various datasets to establish a methodology for the prediction of clearance. Among the examined empirical approaches, an allometric scaling method with the rule of exponent (ROE), based on the exponent in …
Clearance of chrysotile asbestos from human lung
In contrast to amphibole asbestos, chrysotile asbestos fails to accumulate in human lungs. The reason for this phenomenon is not known. To examine this problem, we extracted chrysotile and tremolite fibers from the lungs of 11 chrysotile miners and millers whose last exposure was within 2 years of death and 12 chrysotile miners and millers ...
Selection of the First‐Time Dose in Humans: Comparison of …
The predicted human clearance values were then used to select the estimated starting dose in humans. These doses were then compared with the actual doses given to humans during clinical trials. All four approaches used to estimate the first-time dose in humans provided values that were within the dose range given to humans from …
Determination of the Relative Formation and Elimination Clearance …
Determination of the Relative Formation and Elimination Clearance of Two Major Carbamazepine Metabolites in Humans: A Comparison Between Traditional and Pooled Sample Analysis ... R.J. Determination of the Relative Formation and Elimination Clearance of Two Major Carbamazepine Metabolites in Humans: A Comparison …
Determination of a human hepatic microsomal scaling factor for
Purpose: To determine a microsomal scaling factor for human liver suitable for prediction of in vivo drug clearance from in vitro data and to explore the role of inter-liver variability in this factor on the reported underprediction from microsomal parameters. Methods: Cytochrome P450 (henceforth P450) content in whole homogenates and microsomes from 38 donor …
Renal clearance of perfluorooctane sulfonate and ...
Renal clearance, total clearance, and elimination by menstrual bleedingThe creatine levels in serum and urine were assayed by the alkaline picric acid method (SRL Inc., Japan). Renal clearance (CL R, L/24 h) was calculated as follows: CL R =total amount of creatinine in a 24-h urine sample (μg/24 h)/serum concentration of …
In vitro-in vivo extrapolation and hepatic clearance dependent ...
Introduction. Given that many drugs are primarily eliminated by metabolism, the accurate prediction of hepatic clearance (CL H) is crucial for both evaluating and optimizing new chemical entities as well as estimating first-in-human doses ccessful predictions could help reduce the high attrition 1 associated with the current drug discovery and …
Influence of Intranasal Drugs on Human Nasal Mucociliary Clearance and ...
The nasal mucociliary clearance system, which comprises epithelial cilia and mucus from goblet cells, is an important intrinsic defense mechanism of the upper respiratory tract. ... Influence of Intranasal Drugs on Human Nasal Mucociliary Clearance and Ciliary Beat Frequency Allergy Asthma Immunol Res. 2019 May;11(3):306-319. doi: …
Human airway tuft cells influence the mucociliary clearance …
Respir Res. 2023 Nov 4;24(1):267. doi: ... Application of bitter substances, such as denatonium, led to an increase in mucociliary clearance in human tracheal preparations. This was dependent on activation of the TRPM5 channel and involved cholinergic and nitric oxide signalling, indicating a functional role for human tuft cells in the ...
Persistence or clearance of human papillomavirus infections in ...
All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent.
Evaluation of RES Clearances in Man | SpringerLink
The RES consists of a widely distributed population of fixed and wandering cells which share the common property of being highly phagocytic (Aschoff, 1924). All the cells are mononuclear phagocytes, or macrophages, derived from bone marrow precursors (Langevoort et al, 1970). They have many functions, but tests of RES clearance relate to ...
Interspecies Scaling of Antibody Drug Conjugates (ADC) for …
The objective of this study was to predict human clearance of antibody–drug conjugates (ADC) allometrically from one to three animal species and compare the predicted human clearance with the observed human clearance. For three animal species allometric scaling, the "Rule of Exponents" (ROE) was used. The results of the study indicated ...
Utilization of Liver Microsomes to Estimate Hepatic Intrinsic Clearance ...
Pharm Res. 2017 Jun;34(6):1233-1243. doi: 10.1007/s11095-017-2140-4. ... The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). ...
Determination of a Human Hepatic Microsomal Scaling Factor
Human liver microsomes and, increasingly, hepatocytes, are used widely to assess the metabolic stability of drugs (1,2).Implicit in this practice is the ability to scale in vitro kinetic parameters, e.g., intrinsic clearance, to in vivo pharmacokinetic parameters (3,4).A recent assessment of this procedure based on a compilation of 52 drugs of …
A bodyweight-dependent allometric exponent for scaling clearance …
Purpose: To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug. Methods: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential …
Pharmacokinetics of Caffeine: A Systematic Analysis of Reported …
When comparing saliva-based caffeine clearance against blood-based clearance (Figure 6C) an even stronger correlation of 0.88 with a scaling factor of 01.04 ± 0.02 (x ¯ ± SD) is observed. The integrated clearance data strongly indicates that clearance can either be calculated from saliva or blood-based measurements.
Reticuloendothelial system
In anatomy the term "reticuloendothelial system" (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that effectively clear colloidal vital stains (so called because they stain living cells) from the blood circulation. The term is still used today, but its meaning has changed over the years, and is used inconsistently in present-day literature. Alt…
Evaluation of RES Clearances in Man | Semantic Scholar
The purpose of this chapter is to review critically the methods that are currently available for investigating RE clearance in man and to representative results from studies using each of the main methods. The RES consists of a widely distributed population of fixed and wandering cells which share the common property of being highly phagocytic (Aschoff, …
Evaluation of the clearance characteristics of bioadhesive
This paper describes the characterisation, radiolabelling and clearance characteristics of three bioadhesive nasal delivery systems; starch microspheres, chitosan microspheres and chitosan solution. The time taken for 50% of these bioadhesive materials and a control to be cleared from the nasal cavity, after nasal administration to human ...
Prediction of metabolic clearance using fresh human ...
1. Predictions of in vivo intrinsic clearance from cryopreserved human hepatocytes may be systematically low. In the current study, the metabolite kinetics of a series of CYP3A4 substrates (benzodiazepines) in fresh human hepatocytes from five donors, via a major UK supplier, were investigated and compared with those previously reported (by the authors'' …
Estimating renal and hepatic clearance rates of organophosphate …
The theoretical and practical aspects of predicting clearance from human liver microsomal intrinsic clearance data are described, a summary of advantages and shortcomings of this in vitro system, a synopsis of recent applications, and a discussion of potential future directions for this field are described. Expand
Ext1 heterozygosity causes a modest effect on postprandial lipid ...
Compound heterozygous mice lacking Ldlr and Ext1 showed synergy on plasma TG accumulation and postprandial clearance. In human subjects, a trend was observed in HME patients toward reduced postprandial TG clearance with a concomitant reduction in chylomicron clearance [area under the curve (AUC)-retinyl ester (RE) HME, 844 ± 127 …
Correlation of Plasma Clearance of 54 Extensively ...
Purpose. To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. Methods. Human and rat plasma clearance values …
In Vitro
Accurate prediction of human clearance is of critical importance in drug discovery. In this study, in vitro - in vivo extrapolation (IVIVE) of hepatic clearance was established using large sets of compounds for four preclinical species (mouse, rat, dog, and non-human primate) to enable better understanding of clearance mechanisms and human translation.
Interlaboratory Variability in Human Hepatocyte Intrinsic Clearance ...
Purpose To examine the interlaboratory variability in CLint values generated with human hepatocytes and determine trends in variability and clearance prediction accuracy using physicochemical and pharmacokinetic parameters. Methods Data for 50 compounds from 14 papers were compiled with physicochemical and …
Angiopoietin-like protein 3 governs LDL-cholesterol levels through ...
Angiopoietin-like protein 3 governs LDL-cholesterol levels through endothelial lipase-dependent VLDL clearance J Lipid Res. 2020 Sep;61 ... how ANGPTL3 regulates LDL-C levels is unknown. Here, we demonstrate in hyperlipidemic humans and mice that ANGPTL3 controls VLDL catabolism upstream of LDL. Using kinetic, lipidomic, and …
The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance ...
Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated.
Prediction of Human Drug Clearance from
Purpose. The aim of this study is to compare the accuracy of five methods for predicting in vivo intrinsic clearance (CLint) and seven for predicting hepatic clearance (CLh) in humans using in vitro microsomal data and/or preclinical animal data. Methods. The human CLint was predicted for 33 drugs by five methods that used either in vitro …
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