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Pharmacokinetics is one of the many disciplines that contribute to the discovery and development of drugs. This was not always the case. Although the basic mathematics of pharmacokinetics were described in some detail almost 60 years ago [1,2], about 30 years went by before pharmacokinetics and the closely related discipline of drug metabolism started to make an appreciatable contribution to the understanding and management of drug action and also to the contents of applications to regulatory authorities for drug marketing. The rapid advances in the disciplines of pharmacokinetics and drug metabolism during the 1960s were a result of the combined influences of improved analytical methodology and the increased awareness by health care providers of the fundamental importance of pharmacokinetics in drug development and therapy. The major leap forward in pharmacokinetics during that period was due also to the ingenuity, foresight, and entrepreneurial skills of a number of scientists, predominantly in the United States, including Benet [3], Garrett [4], Gibaldi [5], Levy [6], Riegelman [7], and Wagner [8]. The combined influence of these individuals, and some others, provided a considerable driving force for the rapid evolution of pharmacokinetics. |
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Prior to 1960, pharmacokinetic data made only a minor contribution to regulatory marketing submissions. There was little appreciation of the importance of this type of information, little means to provide pharmacokinetic information in sufficient depth and detail, and the data could not be produced with sufficient speed to make a meaningful contribution, even when it was appreciated. The situation has changed remarkably since then. Pharmacokinetics and metabolism material is not only covered exclusively in several sections of regulatory marketing submissions, worldwide, but is also distributed throughout other sections of the documents to provide support for pharmacology, toxicology, and clinical material. In fact, toxicokinetics has emerged as a major new discipline, bridging toxicology and pharmacokinetics, and continues to play an ever-increasing role in the interpretation of toxicology data and prediction of toxicity profiles in animal species to humans. |
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The phenomenal growth of pharmacokinetics, toxicokinetics, and metabolism in pharmaceutical discovery and development research, from virtually nothing to providing major contributions, can be compared to the almost parallel growth of biotechnology. All of these disciplines have evolved rapidly and now make major contributions to pharmaceutical research and development (R & D). However, biotechnology has evolved in a well-defined discovery environment and has been marked by both successes and failures in the development of biologically based therapeutic agents. Pharmacokinetics, on the other hand, has no discrete boundaries. It contributes across the entire spectrum of activities ranging from early discovery to marketing authorization submission, |
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