Absorption, Distribution, Metabolism, and Excretion of Biopharmaceutical Drug Products

Biopharmaceuticals are playing an increasing role in therapy; as a subset of therapeutics, their proportional use relative to traditional small drugs is increasing in terms of sales and volume. Often termed biotherapeutics, this drug class is primarily represented by protein pharmaceuticals, which includes a wide range of drug sizes covering 1000–150,000 dalton (Da) molecular weight. Given their relatively large size and their hydrophilic nature and susceptibility to hydrolytic degradation in tissues throughout the body (as opposed to primarily renal and hepatic elimination of small drugs), their absorption, distribution, metabolism, and excretion (ADME) properties are different in many aspects. This chapter will describe these properties in detail for protein biopharmaceuticals. This presentation will include strategies to mitigate their susceptibility to hydrolysis in order to increase their bioavailability and prolong their residence time in the body. As well, the important role of modification of the physicochemical properties of proteins in influencing rate of their absorption and exposure-time profile will be discussed in the context of insulin and insulin analogs for the treatment of diabetes mellitus. The chapter will conclude with a relatively brief discussion of the ADME properties of heparin, a carbohydrate-based biopharmaceutical, and those associated with the combined cell- and gene-based therapy of two recently marketed products for the treatment of refractory blood-borne cancers.