PHARMACOKINETIC STUDIES IN HEALTHY-VOLUNTEERS IN THE CONTEXT OF INVITRO INVIVO CORRELATIONS

A multitude of in vivo variables can influence systemic drug absorptio n after intake of an oral formulation. For the measurement of consiste nt in vivo parameters within and between pharmacokinetic studies it is of primary importance that such variables be recognized. Consequently , as many variables as possible should be eliminated or controlled by proper study designs to prevent (or minimize) their disturbance of in vitro/in vivo correlations. The possible influences of some important variables are elaborated and discussed in this paper. The influences o f food can be anticipated and controlled against the background of gas trointestinal physiology with and without food and its interplay with the dosage form. Food, and also posture, and exercise, may influence s planchnic-hepatic blood flow which may substantially affect the absorp tion of drugs with a high first-pass metabolism. The influence of the discussed variables may be modified by the, dosage form of a particula r drug. Single dose studies are appropriate for studying immediate rel ease formulations and in the development of controlled release formula tions. Multiple dose studies are preferred for the formal validation o f controlled release formulations.