Volunteers, healthy assessment methods used

ASSESSMENT METHODS USED IN DRUG EXPERIMENTS ON HEALTHY VOLUNTEERS... 

There are also other BE-type assessments. Interaction studies assess the influence on bioavailability by other individual factors, such as food, alcohol, or other drugs. Such studies are usually single-sequence crossover, but the assessment method remains the same—whether confidence intervals of AUC and Cmax ratios fall within (0.80, 1.25). The same can be said of PK similarity assessments between subject populations, for example, healthy volunteers versus patients. The assessment method is the same as that used for BE, but important differences remain. In typical BE studies, subjects are densely sampled so that individual PK parameters, AUC and Cmax, can be determined with precision. PK similarity assessments are concerned with the differences in different populations, instead of formulations. The assessments are usually based on multiple (parallel) studies, as crossover studies are not possible, and sequence and period effects are not considered. Assessments involve obtaining estimates of average PK parameters in the populations and the 90% confidence intervals for the ratios of the average PK parameters. 

The impact of flow-dependency on pulmonary deposition has been assessed for Rotahaler in healthy volunteers using the charcoal block method the use of a low and high inhalation flow resulted in a pulmonary deposition of 3.6 and 7.0%, respectively of the nominal dose (85). Studies with Turbuhaler have yielded depositions ranging from 16.8% in a first study and between 20 and 27% in later studies, when an inhalation flow of approximately 60 L/ntin was applied (72,86,87). Pulmonary deposition was reduced by half once the inhalation flow fell below 30 L/min (72). 

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