Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. (+info)
Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation.
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One major challenge facing today's cancer researchers and toxicologists is the development of new approaches for the identification of carcinogens and other environmental hazards. Here, we describe the potential impact of emerging technologies for measuring gene expression profiles on carcinogen identification and on the general field of toxicology. An example of one of these technologies is the use of cDNA microarray chips. We provide an overview to the key questions that are confronting investigators charged with determining the relative safety of natural or synthetic chemicals to which humans are exposed, followed by a discussion of how cDNA microarray technology may be applied to these questions. Gene chip technology is still a relatively new technology, and only a handful of studies have demonstrated its utility. However, as the technical hurdles to development are passed, the use of this methodology in addressing the questions raised here will be critical to increase the sensitivity of detection of the potential toxic effects of environmental chemicals and to understand their risks to humans. (+info)
Journal impact factors: a 'bioequivalence' issue?
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AIMS: Journal impact factors (IMFs) are used increasingly by institutions as performance indicators of the quality of 'individual research output'. Although the need for discretion when using the numbers has been emphasized, there has been little formal analysis of the issues. We therefore investigated citation profiles for three clinical pharmacology journals to assess the validity of using IMF as a measure of 'individual research'. METHODS: We compared the pattern of individual citations for random samples of 120 papers published in Clin Pharmacol Ther (CPT), Br J Clin Pharmacol (BJCP) and Eur J Clin Pharmacol (EJCP) in 1981, 1991, 1995 and 1996. Using an analogy between citation-time profiles of papers and concentration-time profiles of drugs, it was possible to define 'lag-time', Cmax, tmax, t(1/2) and AUC(t), and to investigate 'bioequivalence'. RESULTS: Citation distributions for individual publications were widely variable and skewed (skewness = 1.47, 2.16 and 1.37 for CPT, BJCP and EJCP, respectively). The 90% CI values for the IMF of a publication in each journal (i.e. 90% CI for an observation as opposed to 90% CI for the mean) were 0.24-16.94, 0.08-10.3 and 0.09-5.68. CONCLUSIONS: IMF does not represent the impact of an individual paper. Furthermore, if the comparison of journals is treated as a bioequivalence issue, the citation data should be log transformed prior to calculating IMF such that they represent the likelihood of citation for the median article. After such transformation, absolute differences between the IMF of clinical pharmacology journals become much smaller. (+info)
Best practice in therapeutic drug monitoring.
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It is the goal of Therapeutic Drug Monitoring (TDM) to use drug concentrations to manage a patient's medication regime and optimise outcome. Limited resources require that drug assays should only be performed when they do contribute to patient management. For this to be the case a therapeutic drug monitoring service has a far greater role than just therapeutic drug measuring. This article describes the roles and functions of a Best Practice TDM service. The features which can and should be strived for in each step of the TDM process-the decision to request a drug level, the biological sample, the request, laboratory measurement, communication of results by the laboratory, clinical interpretation and therapeutic management-are discussed. (+info)
Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. (+info)
Therapeutic drug monitoring in a developing country: an overview.
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Therapeutic Drug Monitoring (TDM) was introduced in India in the mid and late 1980s and the last 10 years have seen it grow, together with the growth of separate Clinical Pharmacology departments. The TDM service in the country is broadly of two types: in large teaching hospitals where the service is available through departments of Clinical Pharmacology, and in the private sector, where drug estimations are done by clinical biochemistry departments with minimal interpretation. This article is based on literature review and our own experiences over a 10 year period in a department of Clinical Pharmacology. It focuses on the evolution of TDM, its problems such as lack of funding, special aspects such as the impact of ethnic differences, nutritional deficiencies, quality of medicines and availability of generic products; its utility as a research tool and its future. (+info)
Searching for pharmacogenomic markers: the synergy between omic and hypothesis-driven research.
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With 35,000 genes and hundreds of thousands of protein states to identify, correlate, and understand, it no longer suffices to rely on studies of one gene, gene product, or process at a time. We have entered the "omic" era in biology. But large-scale omic studies of cellular molecules in aggregate rarely can answer interesting questions without the assistance of information from traditional hypothesis-driven research. The two types of science are synergistic. A case in point is the set of pharmacogenomic studies that we and our collaborators have done with the 60 human cancer cell lines of the National Cancer Institute's drug discovery program. Those cells (the NCI-60) have been characterized pharmacologically with respect to their sensitivity to >70,000 chemical compounds. We are further characterizing them at the DNA, RNA, protein, and functional levels. Our major aim is to identify pharmacogenomic markers that can aid in drug discovery and design, as well as in individualization of cancer therapy. The bioinformatic and chemoinformatic challenges of this study have demanded novel methods for analysis and visualization of high-dimensional data. Included are the color-coded "clustered image map" and also the MedMiner program package, which captures and organizes the biomedical literature on gene-gene and gene-drug relationships. Microarray transcript expression studies of the 60 cell lines reveal, for example, a gene-drug correlation with potential clinical implications--that between the asparagine synthetase gene and the enzyme-drug L-asparaginase in ovarian cancer cells. (+info)
Candidate genes and single nucleotide polymorphisms (SNPs) in the study of human disease.
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The genomic revolution has generated an extraordinary resource, the catalog of variation within the human genome, for investigating biological, evolutionary and medical questions. Together with new, more efficient platforms for high-throughput genotyping, it is possible to begin to dissect genetic contributions to complex trait diseases, specifically examining common variants, such as the single nucleotide polymorphism (SNP). At the same time, these tools will make it possible to identify determinants of disease with the expectation of eventually, tailoring therapies based upon specific profiles. However, a number of methodological, practical and ethical issues must be addressed before the analysis of genetic variation becomes a standard of clinical medicine. The currents of variation in human biology are reviewed here, with a specific emphasis on future challenges and directions. (+info)