Publication:

Pharmacokinetic availability of proteolytic enzymes after oral administration: a narrative review of the literature

Orally administered serine and cysteine proteolytic enzymes are used extensively in the therapy of various inflammatory conditions. However, due to their protein nature, there have been concerns about these enzymes undergoing digestion or biotransformation in the gut and the resultant amount of active enzyme reaching blood circulation and at the site of inflammation. Research has shown that orally administered serine and cysteine proteases are able to pass through the mucosal barrier of the gastrointestinal tract and reach the blood and lymph as intact, high molecular weight and physiologically active forms. These have been studied in in vitro, animal models and further confirmed in human studies. Despite high inter-individual variability, the maximum plasma levels of the free proteases follow dose linearity. They circulate bound to plasma anti-proteases and are detectable in clinically significant concentrations. Targeted studies also indicate that paracellular transport mechanism may play a significant role in the absorption of these molecules. We present a summary of the existing knowledge from these studies.