Pharmacokinetic studies of protein drugs: past, present and future.

Among the growing number of therapeutic proteins on the market, there is an emergence of biotherapeutics designed from our comprehension of the physiological mechanisms responsible for their peripheral and tissue pharmacokinetics. Most of them have been optimized to increase their half-life through glycosylation engineering, polyethylene glycol conjugation or Fc fusion. However, our understanding of biological drug behaviors is still its infancy compared to the huge amount of data regarding small molecular weight drugs accumulated over half a century. Unfortunately, therapeutic proteins share few resemblances with these drugs. For instance drug-targeted-mediated disposition, binding to glycoreceptors, lysosomal recycling, large hydrodynamic volume and electrostatic charge are typical critical characteristics that cannot be derived from our anterior knowledge of classical drugs. However, the numerous discoveries made in the two last decades have driven and will continue to drive new options in biochemical engineering and support the design of complex delivery systems. Most of these new developments will be supported by novel analytical methods for assessing in vitro or in vivo metabolism parameters.