PRODRUGS, P.Valentina. Bookhata Pharmacy PDF books for students free download

 

PRODRUGS




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1. INTRODUCTION

A prodrug is a chemically inert drug precursor, which upon biotransformation liberates the pharmacologically active parent compound. A prodrug is also called proagent, bio reversible derivative, latentiated drug and congeners.

Drug + cap = prodrug (Released at the site of action).


2. UTILITY OF PRODRUG

There are numerous reasons why one may wisgh to utilize a prodrug strategy in drug design. 

For example:


Solubility :-  

Consider an active drug that is insufficiently soluble in water so that it cannot be injected in a small dose. A water-soluble group could be attached which could be metabolically released after drug administration.

Absorption and Distribution :- 

If the drug is not absorbed and transported to the target site in sufficient concentration, it can be made more water-soluble or lipid soluble, depending on the desired site of action. Once absorption has occurred or when the drug is at the appropriate site of action, the water or lipid soluble group is removed enzymatically.

Site Specificity :- 

Specificity for a particular organ or tissue can be made if there are high concentrations of uniqueness of enzymes present at that site which can cleave the appropriate appendages from the prodrug and unmask the drug

Instability :- 

A drug may be rapidly metabolized and rendered inactive prior, when it reaches the site of action. The structure may be modified to block that metabolism until the drug is at the desired site.

Prolonged Release :- 

It may be desirable to have a steady low concentration of a drug released over a long period of time. The drug may be altered so that it is metabolically converted to the active form slowly.

Toxicity :- 

A drug may be toxic in its active form and would have a greater therapeutic index if it were administered in a nontoxic, inactive form that can be converted to the active form only at the site of action.

Poor Patient Acceptability :- 

An active drug may have an unpleasant taste or odor, produce gastric irritation, or cause pain when administered (e.g., when injected). The structure of the drug can be modified to alleviate these problems, but once administered; the altered drug can be metabolized to the active drug.

Formulation Problems :- 

If the drug is a volatile liquid, it would be more desirable to prepare it in a solid form so that it could be formulated as a tablet. An inactive solid derivative could be prepared which would be converted in the body to the active drug,



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