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NONMEM
NONMEM is a non-linear mixed-effects modeling software package developed by Stuart L. Beal and Lewis B. Sheiner in the late 1970s at University of California, San Francisco, and expanded by Robert Bauer at Icon PLC. Its name is an acronym for NON-linear mixed effects modeling but it is especially powerful in the context of population pharmacokinetics, pharmacometrics, and PK/PD models. NONMEM models are written in NMTRAN, a dedicated model specification language that is translated into FORTRAN, compiled on the fly and executed by a command-line script. Results are presented as text output files including tables. There are multiple interfaces to assist modelers with housekeeping of files, tracking of model development, goodness-of-fit evaluations and graphical output, such as PsN and xpose and Wings for NONMEM. Current version for NONMEM is 7.5. Model estimation NONMEM estimates its models according to principles of maximum likelihood estimation. nonlinear mixed-effects mo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-linear Mixed-effects Modeling Software
Nonlinear mixed-effects models are a special case of regression analysis for which a range of different software solutions are available. The statistical properties of nonlinear mixed-effects models make direct estimation by a BLUE estimator impossible. Nonlinear mixed effects models are therefore estimated according to Maximum Likelihood principles. Specific estimation methods are applied, such as linearization methods as first-order (FO), first-order conditional (FOCE) or the laplacian (LAPL), approximation methods such as iterative-two stage (ITS), importance sampling (IMP), stochastic approximation estimation (SAEM) or direct sampling. A special case is use of non-parametric approaches. Furthermore, estimation in limited or full Bayesian frameworks is performed using the Metropolis-Hastings or the NUTS algorithms. Some software solutions focus on a single estimation method, others cover a range of estimation methods and/or with interfaces for specific use cases. General-pur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Population Pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Overview Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
University Of California, San Francisco
The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It conducts research and teaching in medical and biological sciences. UCSF was founded as Toland Medical College in 1864. in 1873, it became affiliated with the University of California as its Medical Department. In the same year, it incorporated the California College of Pharmacy and in 1881 it established a dentistry school. Its facilities were located in both Berkeley and San Francisco. In 1964, the school gained full administrative independence as a campus of the UC system, headed by its own chancellor, and in 1970 it gained its current name. Historically based at Parnassus Heights with satellite facilities throughout the city, UCSF developed a second major campus in the newly redeveloped Mission Bay district in the early 2000s. '' U.S. N ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nonlinear Mixed-effects Model
Nonlinear mixed-effects models constitute a class of statistical models generalizing linear mixed-effects models. Like linear mixed-effects models, they are particularly useful in settings where there are multiple measurements within the same statistical units or when there are dependencies between measurements on related statistical units. Nonlinear mixed-effects models are applied in many fields including medicine, public health, pharmacology, and ecology. Definition While any statistical model containing both fixed effects and random effects is an example of a nonlinear mixed-effects model, the most commonly used models are members of the class of nonlinear mixed-effects models for repeated measures :_ = f(\phi_,_) + \epsilon_,\quad i =1,\ldots, M, \, j = 1,\ldots, n_i where *M is the number of groups/subjects, *n_i is the number of observations for the ith group/subject, *f is a real-valued differentiable function of a group-specific parameter vector \theta_ and a covariat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacometrics
Pharmacometrics is a field of study of the methodology and application of models for disease and pharmacological measurement. It uses mathematical models of biology, pharmacology, disease, and physiology to describe and quantify interactions between xenobiotics and patients (human and non-human), including beneficial effects and adverse effects. It is normally applied to quantify drug, disease and trial information to aid efficient drug development, regulatory decisions and rational drug treatment in patients. Pharmacometrics uses models based on pharmacology, physiology, and disease for quantitative analysis of interactions between drugs and patients. This involves Systems pharmacology, pharmacokinetics, pharmacodynamics and disease progression with a focus on populations and variability. Mould and Upton provide an overview of basic concepts in population modeling, simulation, and model-based drug development. A major focus of pharmacometrics is to understand variability in dru ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PK/PD Models
PK/PD modeling (pharmacokinetic/pharmacodynamic modeling) (alternatively abbreviated as PKPD or PK-PD modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics. It integrates a pharmacokinetic and a pharmacodynamic model component into one set of mathematical expressions that allows the description of the time course of effect intensity in response to administration of a drug dose. PK/PD modeling is related to the field of pharmacometrics. Central to PK/PD models is the concentration-effect or exposure-response relationship. A variety of PK/PD modeling approaches exist to describe exposure-response relationships. PK/PD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model. However, if a delay is observed between the drug administration and the drug effect, a temporal dissociation needs to be taken into account and more complex models exist: * Direct vs Indirect ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Modeling Language
A modeling language is any artificial language that can be used to express information or knowledge or systems in a structure that is defined by a consistent set of rules. The rules are used for interpretation of the meaning of components in the structure. Overview A modeling language can be graphical or textual. * ''Graphical'' modeling languages use a diagram technique with named symbols that represent concepts and lines that connect the symbols and represent relationships and various other graphical notation to represent constraints. * ''Textual'' modeling languages may use standardized keywords accompanied by parameters or natural language terms and phrases to make computer-interpretable expressions. An example of a graphical modeling language and a corresponding textual modeling language is EXPRESS. Not all modeling languages are executable, and for those that are, the use of them doesn't necessarily mean that programmers are no longer required. On the contrary, executab ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Maximum Likelihood Estimation
In statistics, maximum likelihood estimation (MLE) is a method of estimating the parameters of an assumed probability distribution, given some observed data. This is achieved by maximizing a likelihood function so that, under the assumed statistical model, the observed data is most probable. The point in the parameter space that maximizes the likelihood function is called the maximum likelihood estimate. The logic of maximum likelihood is both intuitive and flexible, and as such the method has become a dominant means of statistical inference. If the likelihood function is differentiable, the derivative test for finding maxima can be applied. In some cases, the first-order conditions of the likelihood function can be solved analytically; for instance, the ordinary least squares estimator for a linear regression model maximizes the likelihood when all observed outcomes are assumed to have Normal distributions with the same variance. From the perspective of Bayesian inference, M ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nonlinear Mixed-effects Model
Nonlinear mixed-effects models constitute a class of statistical models generalizing linear mixed-effects models. Like linear mixed-effects models, they are particularly useful in settings where there are multiple measurements within the same statistical units or when there are dependencies between measurements on related statistical units. Nonlinear mixed-effects models are applied in many fields including medicine, public health, pharmacology, and ecology. Definition While any statistical model containing both fixed effects and random effects is an example of a nonlinear mixed-effects model, the most commonly used models are members of the class of nonlinear mixed-effects models for repeated measures :_ = f(\phi_,_) + \epsilon_,\quad i =1,\ldots, M, \, j = 1,\ldots, n_i where *M is the number of groups/subjects, *n_i is the number of observations for the ith group/subject, *f is a real-valued differentiable function of a group-specific parameter vector \theta_ and a covariat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Numerical Software
Numerical analysis is the study of algorithms that use numerical approximation (as opposed to symbolic manipulations) for the problems of mathematical analysis (as distinguished from discrete mathematics). It is the study of numerical methods that attempt at finding approximate solutions of problems rather than the exact ones. Numerical analysis finds application in all fields of engineering and the physical sciences, and in the 21st century also the life and social sciences, medicine, business and even the arts. Current growth in computing power has enabled the use of more complex numerical analysis, providing detailed and realistic mathematical models in science and engineering. Examples of numerical analysis include: ordinary differential equations as found in celestial mechanics (predicting the motions of planets, stars and galaxies), numerical linear algebra in data analysis, and stochastic differential equations and Markov chains for simulating living cells in medicine and b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for example, infection). Pharmacodynamics and pharmacokinetics are the main branches of pharmacology, being itself a topic of biology interested in the study of the interactions between both endogenous and exogenous chemical substances with living organisms. In particular, pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects. Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference (for example, when speaking of PK/PD models). Pharmacodynamics places particular emphasis on dose–response relationships, that is, the relationships between d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
