Pharmacokinetics and Pharmacodynamics Lecture 5

Study Notes

Pharmacokinetics and Pharmacodynamics of Peptide and Protein Drugs

Pharmacokinetics describes the time course of a drug in a body fluid, preferably plasma or blood, that results from the administration of a certain dosage regimen.
It comprises all processes affecting drug distribution, metabolism, and excretion, absorption.
Pharmacokinetics characterizes what the body does to the drug.

Pharmacokinetics vs Pharmacodynamics

Pharmacodynamics characterizes the intensity of a drug effect or toxicity resulting from certain drug concentration in a body fluid, usually at the assumed site of drug action.
Pharmacodynamics can be simplified to what the drug does to the body.

Protein Bound Drug

Plasma concentration and tissue bound drug concentrations are related to pharmacological response and biochemical events.
Elimination and post-receptor events also play a role in pharmacodynamics.

Pharmacokinetics of Protein Therapeutics

The in vivo disposition of peptide and protein drugs may often be predicted to a large degree from their physiological function.
Peptides, such as hormones, have short elimination half-lives, which is desirable for close regulation of their endogenous levels and function.
Insulin, for example, shows dose-dependent elimination with a relatively short half-life of 25 and 52 minutes at 0.1 and 0.2 U/kg, respectively.
Albumin and immunoglobulins, with transport tasks, have elimination half-lives of several days, enabling continuous maintenance of physiologically necessary concentrations in the bloodstream.

Absorption of Protein Therapeutics

Enteral administration of peptides and proteins is not therapeutically active due to high gastrointestinal enzyme activity and low permeability mucosa.
The lack of systemic bioavailability is mainly caused by these two factors.
Molecular size is generally considered the ultimate obstacle to oral administration.
Oral administration is still a desired route of delivery for protein drugs due to convenience, cost-effectiveness, and painlessness.

Strategies to Overcome Obstacles Associated with Oral Delivery of Proteins

Encapsulation into micro- or nanoparticles to protect proteins from intestinal degradation.
Chemical modifications, such as amino acid backbone modifications and chemical conjugations, to improve resistance to degradation and permeability of protein drugs.
Coadministration of protease inhibitors to inhibit enzymatic degradation.

Parenteral Administration

Most peptide and protein drugs are currently formulated as parenteral formulations due to poor oral bioavailability.
Major routes of administration include intravenous (IV), subcutaneous (SC), and intramuscular (IM) administration, and sometimes intraparentral (IP).
IV administration achieves the highest concentration in the biologic system, while IM or SC injections may be more appropriate for achieving biologic activity of the product.

Description

This quiz covers the pharmacokinetics and pharmacodynamics of peptide and protein drugs, focusing on the dose-concentration-effect relationship and the central paradigm of clinical pharmacology. Understand the time course of a drug in the body and the processes that affect its distribution and metabolism.