Abstract
After being absorbed, drugs distribute in the body in part to reach target tissues, in part to be disposed in tissues where they do not exert clinically-relevant effects. Therapeutically-relevant effects are usually terminated by drug metabolism and/or elimination. The role that has been traditionally ascribed to the spleen in these fundamental pharmacokinetic processes was definitely marginal. However, due to its high blood flow and to the characteristics of its microcirculation, this organ would be expected to be significantly exposed to large, new generation drugs that can hardly penetrate in other tissues with tight endothelial barriers. In the present review, we examine the involvement of the spleen in the disposition of monoclonal antibodies, nanoparticles and exosomes and the possible implications for their therapeutic efficacy and toxicity. The data that we will review lead to the conclusion that a new role is emerging for the spleen in the pharmacokinetics of new generation drugs, hence suggesting that this small, neglected organ will certainly deserve stronger attention by pharmacologists in the future.
Highlights
“What does that do a spleen?” asked Charles Freck to Jim Barris in the famous novel “A Scanner Darkly” by Philip K
We will go through the evidence showing that the spleen may affect the disposition of monoclonal antibodies, nanoparticles and exosomes contributing to their clearance, and representing, in selected cases, an important target organ where their pharmacological effects are exerted
The data that we reviewed in the present paper clearly indicate that because of its anatomical characteristics, such as its high blood flow and loose capillaries, the spleen is highly exposed to circulating drugs
Summary
“What does that do a spleen?” asked Charles Freck to Jim Barris in the famous novel “A Scanner Darkly” by Philip K. The little attention paid to the spleen in pharmacology was probably due to the lack of evidence that it could have a major role in the disposition of the “classical” drugs. We will go through the evidence showing that the spleen may affect the disposition of monoclonal antibodies, nanoparticles and exosomes contributing to their clearance, and representing, in selected cases, an important target organ where their pharmacological effects are exerted. Before addressing these points, we first have to examine the microanatomy characteristics of the spleen that set the structural basis for drug-spleen interaction
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