A short review of the pharmacokinetic behavior of biological medicinal agents for the clinical practice

The absorption and distribution of biological medicinal agents after subcutaneous (sc) and intramuscular injections are influenced by the molecular characteristics of the drug. The large size of the mAbs limits their distribution primarily to the vascular system, their volume of distribution is similar to that of albumin. They are mostly administered by iv injection, however co-administration with recombinant human hyaluronidase derivate (rHuPH20) enables their rapid absorption after subcutaneous administration. Target mediated drug disposition (TMDD) is the main mechanism of the elimination of the biological macromolecules. The plasma half-lives of IgG based mAbs are determined by their binding to the neonatal Fc receptors (FcRn) protecting them from proteolysis in the endosomes. When the endosomes recirculate to the cell surface the mAb will be released back into the circulation. This mechanism is responsible for their unusually long (> 10 days) half-lives. The excretion of the drug proteins proceeds through catabolization to smaller peptides which are then excreted by the kidney (< 30 kDa), less frequently through the bile, or are further metabolized to amino acids. The amino acids in turn can be reused for protein synthesis. The immune complexes (IC), especially those containing an antidrug antibody (ADA), are rapidly taken up by the Kupffer cells of the liver.