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namic information can be obtained by combining data from various sources during clinical trials in order to identify and predict drug disposition and pharmacokinetic/pharmacodynamic relationships in specific populations. This author does not take issue with these arguments. However, the principal question that needs to be addressed, particularly in the current environment, is whether the mixed effect modeling approach actually adds value in terms of overall efficacy of the clinical drug development program. Regulatory agencies have not helped to resolve this question as their approach varies and often depends on the individuals currently making regulatory decisions. This area is fraught with advocates and skeptics. The degree of enthusiasm for mixed effect modeling almost invariably correlates highly with the mathematical expertise of individuals involved. Again, without taking issue, this writer's opinion is that, in the new cost-conscious drug development environment, mixed effect modeling will continue to be handled on a case-by-case basis and may evolve further as the associated computer software becomes more user friendly and less exclusive in nature. What is more doubtful is the extent to which such analyses become recognized as a necessary component leading to faster marketing approval of a new chemical entity. This hitherto has not been the case, and greater acceptance of the mixed effect approach will depend, to a great extent, on the actual value added relative to conventional approaches. Mixed effect modeling is currently regarded as a supplemental approach to the main thrust of clinical development programs, and specific studies in special populations continue to be the norm, whether associated with pharmacokinetic analysis or with establishing pharmacokinetic-pharmacodynamic relationships. Typical Phase 3 studies involving pharmacokinetics are summarized in Table 3. |
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Most Phase 3 clinical programs include between 4 and 8 drug interaction studies. Such studies, if justified, should always be carried out on the market image dosage form. The outcome of an initial food-drug interaction study may lead to additional studies. For example, if the systemic availability of a drug is |
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| Table 3 Phase 3 Clinical Studies Involving Pharmacokinetics | | Therapeutic drug-level monitoring of safety and efficacy trials | | Special patient populations | | Renal failure | | Hepatic failure | | Elderly versus young | | Drug interactions |  |
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Bioavailability/bioequivalence of market-image versus clinical trial formulations |
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