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| Table 5 Areas of Pharmacokinetic and Drug Metabolism Support That Warrant Greater or Less Emphasis in Clinical Development | | Greater emphasis | | | Early metabolism studies | Duplicative clinical studies | | Absolute bioavailability | Multiple food-effect studies |  |
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Early systemic availability of market-image formulations |
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Unnecessary pharmacokinetic profiling in safety and efficacy studies |
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Pharmacokinetic-pharmacodynamic relationships and mixed effect modeling approaches* |
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Unnecessary and inappropriate interaction studies |
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| | Compound specific. Depends on drug, therapeutic class, and regulatory position. |
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the tendency for companies to include as much data as conceivably possible in regulatory submissions, has led to often unreasonable demands on these disciplines. |
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If this trend were allowed to continue in pharmacokinetics and drug metabolism, as in every other discipline involved in the discovery and development process, then pharmaceutical research and development will rapidly become prohibitively cost ineffective. The recommendations for changes in pharmacokinetic and metabolism involvement described in this chapter are based on observations made during over a decade of experience in the pharmaceutical industry. While many attempts have been made to focus directly on pharmacokinetic and metabolism activities, the argument has frequently expanded, without apology, to other areas, in particular to clinical research where considerable changes and economies in developmental philosophy are needed. Attention has focused primarily on activities that, in the writer's opinion, need to be changed, either expanded or reduced. Other areas, not addressed here, work well and do not represent a burning platform for change [20]. |
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It is worth noting that the objective of pharmacokinetic support for a drug development program should be to provide information that supports safety and efficacy claims. It is not, as appears often to have been assumed, to provide an exhaustively complete and in-depth pharmacokinetic and metabolism profile of a drug candidate under every conceivable situation. In this time of rationalization and need for responsible cost containment, it is imperative that emphasis in utilization of pharmacokinetic and drug metabolism resources be placed not on total pharmacokinetic and pharmacodynamic characterization, but rather on responsible and efficient application of limited resources to provide adequate support to ensure that a safe and efficacious drug is being introduced to the market. |
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