Chapter 5. Pharmacology, Toxicology, Therapeutic Dosage Formulations, and Clinical Response

Summary

This chapter is organized in a format familiar to clinical practitioners and pharmaceutical scientists. The common features of biotechnology products and their underlying pharmacology, toxicology and pharmacokinetic characteristics are discussed under the section on Clinical Pharmacology and Toxicology. In addition to discussion of basic pharmacokinetic principles related to protein biopharmaceuticals and antibody molecules, this section details biopharmaceutical disposition-mechanisms, including absorption and bioavailability, and elimination and metabolism. Mechanisms and potential impact of immunologic responses to biotechnology products are also highlighted. This is followed by discussion on fundamental principles of dose and therapeutic response. The role of therapeutic index related to drug efficacy and safety is also defined in this section. The final section highlights fundamental principles and strategies for dosage formulation. Optimal dosage formulation is needed to ensure that the final therapeutic product is chemically and physically stable in storage and is appropriate for the intended route of administration. Where appropriate, distinctions are made between biotechnology products and traditional, chemical drugs with respect to clinical pharmacology and drug disposition mechanisms.