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Clinical Phases 2 and 3 are periods of close interaction between pharmacokinetics and clinical sciences. It is a period of considerable resource commitment and also the time during which the biggest changes in pharmacokinetic involvement are necessary. |
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Changes in pharmacokinetics resource commitment are a function of the number and types of clinical studies conducted and also the degree of pharmacokinetic involvement in individual studies. Prospective planning among clinical and pharmacokinetic disciplines is essential in order to achieve a more efficient and cost-effective clinical development program. |
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In most programs far too many clinical studies are conducted, sometimes to satisfy one or other opinion leaders in a specific and perhaps isolated market, but often also as a result of poor prospective planning. Regulatory approval of a drug for marketing is generally based on two or three pivotal safety and efficacy studies together with specific pharmacokinetic and/or pharmacodynamic studies such as food effect, interactions, and special populations. Most NDAs (New Drug Applications) contain far in excess of this. Some of the additional studies may be required for particular circumstances but many are wasteful, duplicative, or simply unnecessary. There is generally little reason why the same clinical study should be conducted in more than one country. A single study should be conducted under conditions that meet worldwide regulatory requirements. An extensive series of drug-food interactions studies is wasteful and can be avoided if initial studies are conducted correctly and if market-image formulations are available early in a clinical program. Drug-drug interactions should be limited to the absolute minimum and should be restricted, for the most part, to those interactions that are predicted from preliminary in vitro metabolism or binding screens. The concept of restricting the number of interaction studies would perhaps not be supported by marketing colleagues but is nonetheless mandatory for responsible cost containment. True pharmacologic or therapeutic interactions cannot readily be examined in a study conducted in a small number of subjects or patients and are best determined during large clinical trials, or subsequently during drug therapy. |
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Depending on the type of drug and therapeutic class, complete pharmacokinetic profiles should not be required for any study that is not specifically pharmacokinetically driven. Such data are nice to have but are not necessary for regulatory marketing approval. Drug level monitoring, which may also include metabolite monitoring, during clinical trials should be restrictive and sampling should be limited to that which is absolutely essential. |
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This depends, of course, on the philosophical approach to study design and analysis for a particular compound or compound class. When a conventional approach is used in which specific studies are conducted to characterize drug |
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