Clinical developmental phase

IN addition to covering traditional areas such as mechanism of action, structure-function relationships, and drug disposition and toxicity, this part of the volume reviews drug-specific data that are specifically pertinent to children and adolescents. Age and developmental phase as critical variables relevant to dosing schemes and side effect liabilities are two recurring themes. Clinical mechanics for using these... 

Preliminary Testing Data Any data generated during the developmental and clinical trial phases of the drug may be useful to determine the expected manufacturing process variability. The process variability is an important factor to define the sampling plan to be used in the stability study. 

Only three dalbaheptides are commercialized vancomycin (39) and teicoplanin (18—22) for human health, and avoparcin (63—65) for animal usage. Vancomycin, the main trademark of which is EH Lilly s Vancocin had 1990 sales around 160 million. Total annual production is in the vicinity of 8 t. Teicoplanin, trademarked Targocid, had 1990 sales of 35 million corresponding to 200 kg. Teicoplanin is commercialized in Europe, Hong Kong, Korea, and the Middle East. It is at the late developmental clinical phase in North America and Japan. Avoparcin is used as a growth promoting feed additive (see... 

The described supportive study was specifically designed and suitably powered to identify differences in Drug XYZ pharmacokinetics between obese and non-obese. Typically this type of evaluation would be extended during the later clinical development by performing a population pharmacoki-netic/pharmacodynamic assessment of the impact of obesity on the disposition of the developmental drug during the phase II/III studies. 

A pharmaceutical product must fulfil its purpose under all recommended conditions and it must do so reproducibly. Experience shows that efficacy in controlled experiments does not guarantee that the product does the same and to the same degree under practical conditions. Pharmaceuticals for humans must be tested in human beings for their pharmacodynamic and pharmacokinetic characteristics to prove their effectiveness and safety. These clinical trials are normally carried out in three stages, each phase involving an increased number of patients. Clinical trials in humans are usually the most critical, most expensive, and most time-consuming developmental step and can account for more than one half of the development costs. 

Especially in combination with alternative approaches such as toxicogenom-ics or a phase 0 clinical trial based on microdosing, fish embryo assays have a strong potential for reducing drug developmental costs in the near future.15-109 This is also demonstrated by a growing number of enterprises in which lead development and initial preclinical safety evaluation is performed with embryos... 

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