ABSTRACT
In addition to the assessment of bioequivalence (BE) in average bioavailability (BA) in terms of the pharmacokinetic (PK) responses, such as AUC and Cmax, it is also important to study the behaviors of those PK responses that may provide useful information for evaluation of drug efficacy and safety. For this purpose, some studies related to BA, such as drug interaction studies, dose proportionality studies, steadystate analyses, food-effect BA and fed BE studies, are often conducted to study the behavior of the plasma concentrations in terms of AUC and other PK responses. In practice, it is not uncommon that more than one drug may be given to a patient
at the same time. Therefore, it is important to examine the relative BA of the study drug when it is co-administered with food or other medications. For this purpose, a drug-to-drug interaction study is usually conducted to study the effect of other medications on the study drug and the effect of the study drug on other drugs. On the other hand, a food-effect BA study is usually conducted to assess the potential influence of the food on the rate and extent of absorption of the study drug when it is administrated right after a meal. A study of this kind can certainly provide valuable information on the efficacy or safety of the study drug which should be provided in the drug interactions, warnings and precautions, clinical pharmacology, and dosage and administration sections of the drug label. When a new compound is discovered, it is important to determine an appropriate
dose so that the drug can reach its maximum therapeutic effect with minimum toxicity. If there is a linear relation between AUC and dose, then an optimal dose level can be obtained to reach a desired blood AUC for therapeutic effect. Therefore, it is of interest to determine whether there exists a linear relationship between the PK measures of systemic exposure and the dose level through a dose proportionality (or linearity) study. The objective of a steady-state analysis is to determine whether the plasma
concentrations of the active ingredients of the study drug can reach and maintain at an almost constant level after multiple dosing. This analysis provides useful information for evaluation of drug safety.
