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European Journal of Pharmaceutical... Jul 2012Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble... (Review)
Review
Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble insulin and insulin suspensions in a recent contribution to this journal (Søeborg et al., 2009). In the present article, the absorption kinetics for mixtures of insulins is described. This requires that the bioavailability of the different insulins is considered. A short review of insulin bioavailability and a description of the subcutaneous depot thus precede the presentation of possible mechanisms associated with subcutaneous insulin degradation. Soluble insulins are assumed to be degraded enzymatically in the subcutaneous tissue. Suspended insulin crystals form condensed heaps that are assumed to be degraded from their surface by invading macrophages. It is demonstrated how the shape of the heaps affects the absorption kinetics. Variations in heap formation thus explain some of the additional variability associated with suspended insulins (e.g. NPH insulins) compared to soluble insulins. The heap model also describes how increasing concentrations of suspended insulins lead to decreasing bioavailability and lower values of Cmax. Together, the findings constitute a comprehensive, quantitative description of insulin absorption after subcutaneous administration. The model considers different concentrations and doses of soluble insulin, including rapid acting insulin analogues, insulin suspensions and biphasic insulin mixtures. The results can be used in both the development of novel insulin products and in the planning of the treatment of insulin dependent diabetic patients.
Topics: Absorption; Animals; Biological Availability; Chemistry, Pharmaceutical; Computer Simulation; Crystallization; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin, Isophane; Models, Biological; Subcutaneous Tissue; Technology, Pharmaceutical; Tissue Distribution
PubMed: 21703346
DOI: 10.1016/j.ejps.2011.06.005 -
Vitamins and Hormones 2007The presence and activity of vitamin E in the organism as well as its role in disease prevention depend, as for any other microconstituent in food, on a number of... (Review)
Review
The presence and activity of vitamin E in the organism as well as its role in disease prevention depend, as for any other microconstituent in food, on a number of factors related to its release from the food matrix, extent of absorption, and metabolic fate. Biotransformation can be defined as the sum of processes in which vitamin E compounds are altered by the body. It involves the bioactivation and production of reactive metabolites, a series of processes generally referred to as "vitamin E metabolism." This chapter will provide an overview of the known and less known steps of vitamin E biotransformation in humans. Due to recent advances related to the biological activities and metabolic processing of vitamin E compounds, particular attention will be given to the description of the formation, identification, and functions of vitamin E metabolites. The hypothesis of a transformation-dependent bioactivation of vitamin E represents an intriguing and emerging aspect of research that deserves further investigation.
Topics: Antioxidants; Biotransformation; Humans; Vitamin E
PubMed: 17628177
DOI: 10.1016/S0083-6729(07)76009-0 -
Advances in Experimental Medicine and... 2014Advances in mass spectrometry, proteomics, protein bioanalytical approaches, and biochemistry have led to a rapid evolution and expansion in the area of mass... (Review)
Review
Advances in mass spectrometry, proteomics, protein bioanalytical approaches, and biochemistry have led to a rapid evolution and expansion in the area of mass spectrometry-based biomarker discovery and development. The last decade has also seen significant progress in establishing accepted definitions, guidelines, and criteria for the analytical validation, acceptance, and qualification of biomarkers. These advances have coincided with a decreased return on investment for pharmaceutical research and development and an increasing need for better early decision making tools. Empowering development teams with tools to measure a therapeutic interventions impact on disease state and progression, measure target engagement, and to confirm predicted pharmacodynamic effects is critical to efficient data-driven decision making. Appropriate implementation of a biomarker or a combination of biomarkers can enhance understanding of a drugs mechanism, facilitate effective translation from the preclinical to clinical space, enable early proof of concept and dose selection, and increase the efficiency of drug development. Here we will provide descriptions of the different classes of biomarkers that have utility in the drug development process as well as review specific, protein-centric, mass spectrometry-based approaches for the discovery of biomarkers and development of targeted assays to measure these markers in a selective and analytically precise manner.
Topics: Animals; Biomarkers; Drug Discovery; Humans; Mass Spectrometry; Pharmacokinetics
PubMed: 24952191
DOI: 10.1007/978-3-319-06068-2_16 -
Current Drug Metabolism 2018Ternary solid dispersions have been demonstrated to be an effective strategy in the improvement of drug absorption and bioavailability. (Review)
Review
BACKGROUND
Ternary solid dispersions have been demonstrated to be an effective strategy in the improvement of drug absorption and bioavailability.
METHOD
The applications of the combination of hydrophilic polymers with the potential of hydrophobic polymer incorporation at moderate concentrations have been discussed in recent publications.
RESULTS
In this paper, the general review of this specific type of solid dispersion will be provided with comprehensive understanding of polymer blends of either hydrophilic or hydrophobic polymers. A detailed description of miscible polymers has been developed in recent studies. In addition to dissolution rate improvement, the role of second polymers in crystal growth inhibition and in maintaining the amorphous state will be mentioned.
CONCLUSION
We also present a summary of characterization techniques commonly used to evaluate solid dispersion and polymer miscibility.
Topics: Biological Availability; Drug Design; Hydrophobic and Hydrophilic Interactions; Pharmaceutical Preparations; Polymers
PubMed: 29956619
DOI: 10.2174/1389200219666180628171100 -
Expert Opinion on Drug Metabolism &... Jan 2011In recent years, interest in paediatric pharmacokinetics has grown. Even though pharmacokinetic and pharmacodynamic relations determine together the optimal drug dose,... (Review)
Review
IMPORTANCE OF THE FIELD
In recent years, interest in paediatric pharmacokinetics has grown. Even though pharmacokinetic and pharmacodynamic relations determine together the optimal drug dose, age-related changes in pharmacokinetics have proven of utmost importance for optimising drug dosing in children.
AREAS COVERED IN THIS REVIEW
Constraints in paediatric studies result in data sets with specific characteristics requiring advanced analysis and validation approaches which are discussed in conjunction with directions for future research.
WHAT THE READER WILL GAIN
Advances have been made in the development of descriptive paediatric pharmacokinetic models for specific drugs and age ranges, and in the identification of analysis and diagnostic tools for paediatric model building and evaluation, while sharing of data between academia and/or industry has proven crucial for limiting additional burden in children. Even though progress is being made, currently none of the scaling approaches has proven of universal value for extrapolations to other age ranges and/or other drugs.
TAKE HOME MESSAGE
The focus of future research should be on the development of mechanistic and validated pharmacokinetic models for specific elimination routes that have predictive and extrapolation potential, making them of use in designing algorithms to derive first-time-in-child doses and individualised dosing guidelines in paediatrics.
Topics: Algorithms; Child; Clinical Trials as Topic; Expert Testimony; Humans; Models, Biological; Pediatrics; Pharmaceutical Preparations; Pharmacokinetics; Research Design
PubMed: 21117982
DOI: 10.1517/17425255.2011.539201 -
European Review For Medical and... 2002Phamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile... (Review)
Review
Phamacokinetics is proposed to study the absorption, the distribution, the biotransformations and the elimination of drugs in man and animals. A single kinetic profile may be well summarized by Cmax, Tmax, t 1/2 and AUC and, having more than one profile, 8 parameters at least, the mean and standard deviation of these parameters, may well summarize the drug kinetics in the whole population. A more carefull description of the data can be obtained interpolating and extrapolating the drug concentrations with some mathematical functions. These functions may be used to reduce all the data in a small set of parameters, or to verify if the hypotheses incorporated in the functions are confirmed by the observations. In the first case, we can say that the task is to get a simulation of the data, in the second to get a model. The functions used to interpolate and reduce the pharmacokinetic data are the multiexponential functions and the reference models are the compartmental models whose solutions are just the multiexponential functions. Using models, new meaningfull pharmacokinetic parameters may be defined which can be used to find relationships between the drug kinetic profile and the physiological process which drive the drug absorption, distribution and elimination. For example, compartmental models allow to define easily the clearance which is dependent on the drug elimination process, or the volume of distribution which depends on the drug distribution in the tissues. Models provide also an easy way to get an estimate of drug absorption after extravasculare drug administration (bioavailability). Model building is a complex multistep process where, experiment by experiment and simulation by simulation, new hypothesis are proven and disproven through a continuous interaction between the experimenter and the computer.
Topics: Algorithms; Animals; Area Under Curve; Biological Availability; Half-Life; Humans; Models, Biological; Pharmacokinetics; Research
PubMed: 12708608
DOI: No ID Found -
AAPS PharmSciTech Jul 2022Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including... (Review)
Review
Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.
Topics: Biological Availability; Catechin; Skin; Skin Absorption; Tea
PubMed: 35798907
DOI: 10.1208/s12249-022-02344-3 -
The Journal of Pharmacology and... May 2011Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements... (Review)
Review
Recent advances in small-animal molecular imaging instrumentation combined with well characterized antibody-labeling chemistry have enabled detailed in vivo measurements of antibody distribution in mouse models. This article reviews the strengths and limitations of in vivo antibody imaging methods with a focus on positron emission tomography and single-photon emission computed tomography and a brief discussion of the role of optical imaging in this application. A description of the basic principles behind the imaging techniques is provided along with a discussion of radiolabeling methods relevant to antibodies. Practical considerations of study design and execution are presented through a discussion of sensitivity and resolution tradeoffs for these techniques as defined by modality, signaling probe (isotope or fluorophore) selection, labeling method, and radiation dosimetry. Images and analysis results from a case study are presented with a discussion of output data content and relevant informatics gained with this approach to studying antibody pharmacokinetics.
Topics: Animals; Antibodies; Diagnostic Imaging; Fluorescence; Image Processing, Computer-Assisted; Luminescence; Mice; Pharmacokinetics; Physics; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon
PubMed: 21317355
DOI: 10.1124/jpet.110.172916 -
British Journal of Pharmacology Sep 2014The delivery of therapeutic agents is characterized by numerous challenges including poor absorption, low penetration in target tissues and non-specific dissemination in... (Review)
Review
The delivery of therapeutic agents is characterized by numerous challenges including poor absorption, low penetration in target tissues and non-specific dissemination in organs, leading to toxicity or poor drug exposure. Several nanomedicine strategies have emerged as an advanced approach to enhance drug delivery and improve the treatment of several diseases. Numerous processes mediate the pharmacokinetics of nanoformulations, with the absorption, distribution, metabolism and elimination (ADME) being poorly understood and often differing substantially from traditional formulations. Understanding how nanoformulation composition and physicochemical properties influence drug distribution in the human body is of central importance when developing future treatment strategies. A helpful pharmacological tool to simulate the distribution of nanoformulations is represented by physiologically based pharmacokinetics (PBPK) modelling, which integrates system data describing a population of interest with drug/nanoparticle in vitro data through a mathematical description of ADME. The application of PBPK models for nanomedicine is in its infancy and characterized by several challenges. The integration of property-distribution relationships in PBPK models may benefit nanomedicine research, giving opportunities for innovative development of nanotechnologies. PBPK modelling has the potential to improve our understanding of the mechanisms underpinning nanoformulation disposition and allow for more rapid and accurate determination of their kinetics. This review provides an overview of the current knowledge of nanomedicine distribution and the use of PBPK modelling in the characterization of nanoformulations with optimal pharmacokinetics.
Topics: Chemistry, Pharmaceutical; Humans; Models, Biological; Nanomedicine; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 24467481
DOI: 10.1111/bph.12604 -
Computers in Biology and Medicine Mar 2019The fate of administered drugs is largely influenced by their metabolism. For example, endogenous enzyme-catalyzed conversion of drugs may result in therapeutic... (Review)
Review
The fate of administered drugs is largely influenced by their metabolism. For example, endogenous enzyme-catalyzed conversion of drugs may result in therapeutic inactivation or activation or may transform the drugs into toxic chemical compounds. This highlights the importance of drug metabolism in drug discovery and development, and accounts for the wide variety of experimental technologies that provide insights into the fate of drugs. In view of the high cost of traditional drug development, a number of computational approaches have been developed for predicting the metabolic fate of drug candidates, allowing for screening of large numbers of chemical compounds and then identifying a small number of promising candidates. In this review, we introduce in silico approaches and tools that have been developed to predict drug metabolism and fate, and assess their potential to facilitate the virtual discovery of promising drug candidates. We also provide a brief description of various recent models for predicting different aspects of enzyme-drug reactions and provide a list of recent in silico tools used for drug metabolism prediction.
Topics: Animals; Computer Simulation; Drug Discovery; Humans; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 30682640
DOI: 10.1016/j.compbiomed.2019.01.008