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While this has been professionally satisfying for practicing pharmacokinetics and drug metabolism scientists, one must ask the following questions: are too many of these types of data being generated for regulatory submissions and can whatever data are truly necessary be generated and handled more efficiently? The answers, in the writer's opinion, are yes on both counts. While kinetic and metabolism information is essential at all stages of a drug discovery and development program, too many data are being collected, often on a nice to know basis, and are too often handled inefficiently. Some pharmacokineticists fall into the trap of using pharmacokinetic data for convenience, as a surrogate, when other data such as clinical pharmacology or therapeutic end-points cannot be readily obtained. Pharmacokinetic data are also not necessarily always easy to obtain. In many cases considerable analytical challenges have to be met before kinetic data can be generated, and correct interpretation of such pharmacokinetic data is often technically difficult. Nonetheless, the end result of pharmacokinetic data analysis is a body of highly quantitative information that can be interpreted, together with other information, to characterize the disposition and also kinetic-dynamic relationships of a compound. Unfortunately, such data are subject to misinterpretation or over interpretation, leading to incorrect or inappropriate conclusions and predictions. For example, poor systemic availability may be used as a basis to discontinue development of a drug candidate. However systemic availability may actually be unimportant depending on the site and mechanism of action, degree of tissue penetration, or a number of other factors that may impact the overall clinical efficacy of a compound. |
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Thus, while pharmacokinetics and drug metabolism are essential components of the discovery and development process, the extent of their utilization needs to be reassessed in terms of their relevance and efficiency of use. The following proposals might help to achieve this goal. |
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Given the pervasive nature of pharmacokinetic and metabolism science involvement in drug discovery and development, it is both logical and necessary for these disciplines to be involved during early planning stages. Too often a pharmacokineticist is required to act quickly to sudden and unexpected requests emanating from events and observations in other disciplines. Such requests are frequently unnecessary and always disruptive in that they require sudden shifts of resources from one program to another. These types of circumstances arise frequently, but could often be avoided if pharmacokinetic perspectives were included in advanced project planning. Resources can then be planned and assigned with reasonable consistency in order to provide optimum support consistent with overall priorities among competing or compli- |
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