Organic Pharmaceutical Chemistry: Prodrugs 2

Organic Pharmaceutical Chemistry IV
1st Semester, Year 5 (2016-2017)
Lecture 2



Organic Pharmaceutical Chemistry:
Prodrugs



Dr Asim A. Balakit
Pharmaceutical Chemistry Dept.,
College of Pharmacy,
Babylon University

This lecture is mainly based on:
Chapter 4, Prodrugs and Drug Latentiation, FORREST T. SMITH AND C. RANDALL CLARK Wilson and Gisvold s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 11th ed., 2004, Lippincott Williams & Wilkins, USA.

This phase can be considered as the phase involving absorption, distribution, metabolism and excretion of the drug.

The pharmacokinetic studies provide valuable information regarding the in vivo properties of a drug’s limitation such as poor absorption, too rapid elimination and pre systemic metabolism.

If these properties can be related back to the physicochemical and dosage form properties of the system, then corrections will require prodrug interventions.

Incomplete absorption of the drug from the delivery system or across biological barriers such as the gastrointestinal mucosal cells and the blood brain barrier.

Incomplete systemic delivery of an agent due to pre-systemic metabolism in the gastrointestinal lumen mucosal cells and liver.

Toxicity problems associated with local irritation or distribution into tissue other than the desired target organ.

Poor site specificity of the drug.

How Can We Use The Prodrug Approach To Overcome Pharmacokinetic Barriers ?!

Absorption Problems:

The drug absorption problems are associated with the physicochemical properties of drug itself.

Bioavailability after oral dosing of various water insoluble agents is often dissolution rate limited.

On the other hand;

Absorption of highly polar agents is often limited by their transport across the GI cell membrane.