Intra-individual variability

This research is an outgrowth of an earlier project which sought to characterize the mechanism of arsenic metabolism in a population currently drinking arsenic-contaminated water in Taiwan. There were three parts to the study, a cohort study, a case control study for skin cancer, and a study of intra-individual variability associated with chronic arsenic exposure. The latter three research projects are complete and being submitted for publication. The results of this research are highly relevant since they indicate that alterations in methylation capacity may affect arsenic carcinogenesis. 

Balogh, A., Harder, S., Vollandt, R. and Staib, A.H. (1992) Intra-individual variability of caffeine elimination in healthy subjects. International Journal of Clinical Pharmacology, Therapy, and Toxicology, 30 (10), 383—387. 

Intra-individual variability, for example due to up- or downregulation of various proteins after multiple dosing, including receptors, carriers and enzymes, resulting in, amongst other effects, the development of tolerance. 

Heinemann L, Klappoth W, Rave K, Hompesch B, Linkeschowa R, Heise T. Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer. Diabetes Care 2000 23(9) 1343-7. 

Intra-individual variability Biological variation within people. Interindividual variability Biological variation between people. 

Khan, T. et al. Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Br J Haematol 2004,124 348-354. 

To illustrate the type of data that can be obtained using the discussed study, a high level summary of the data from the study described above under Procedure is presented below. It should be noted that in this specific example-study for the first application in man, only a liquid formulation was available, which - due to low solubility of the drug - generated notable inter- (and intra-) individual variability. 

Mixed effect modeling deals with the situation in between. Inter and intra individual variability are separated and calculated within the same step. Inter individual random effects are calculated for those parameters for which this information can be drawn from the data set. In general only one residual error is calculated. The method is very well suited for sparse and unbalanced data situations. 

In recent years, varions dmgs have been developed for the treatment of the human immunodeficiency vims (HIV) infection. The two most important compound classes are the HIV selective protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTI), and the non-nucleoside reverse transcriptase inhibitors (tiNRTI). Methods developed for TDM of these compounds are discussed here. TDM is required because of a high inter- and intra-individual variability. 

Of the various dehydrogenases, glutamate dehydrogenase (GLDH) can be a good indicator for mitochondrial damage in juvenile rats. However, this measurement has less value in older rats, where there is greater inter- and intra-individual variability (O Brien et al. 2002). 

Fraser AG, RosaDd SB, Gamble GD, Pounder RE. Inter-individual and intra-individual variability of ethanol ccncentiation-time profiles ccmpaiison of ethanol ii estion before or after an evenii meal BrJ Chn Pharmacol (1995) 40,387—92. 

Inter-Individual versus Intra-Individual Variability... 

An important and often overlooked distinction that has led to confusion in the literature is that between inter-individual and intra-individual variability. That is, relationships that exist among individuals may not be the same as those relationships that exist within individuals. From a research design perspective, it is important to be clear which of these associations is being investigated. A common mistake is to formulate a hypothesis concerning an intra-individual association, say, on the effects of different treatments on an individual s blood pressure, but to conduct an experiment in which each person receives a difierent treatment or manipulation. 

Furthermore, recent statistical advances have expanded the repertoire of tools with which to analyze data tfom these designs. For example, hierarchical linear models (J. E. Schwartz, Warren, Pickering, 1994), random regression models (Jacob et al., in press), or pooled cross-sectional time series (Dielman, 1983) allow for the partitioning of inter-individual and intra-individual variability from a number of different sources. Complemented by iet a a/vric techniques that allow for the examination of multiple dependent variables (Cohen, 1982), these methods offer many data analytic strategies for multivariate, replicated, repeated-measures, singlesubject designs. Several of these techniques are illustrated in the next section. 

The intra-individual variability of reaction time Introduction... 

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