Understanding Prodrugs: Which of the following is not a pro drug?

October 12, 2025 •

4 min read

Approximately 10% of all medicines available worldwide are classified as prodrugs [1.2.1]. To understand the common pharmacology question, 'Which of the following is not a pro drug?', it's essential to first grasp what a prodrug is and how it differs from a conventional active drug.

Quick Summary

A prodrug is an inactive medication that the body converts into an active drug through metabolism. This contrasts with active drugs, which are effective upon administration. Key examples help differentiate them.

Key Points

Definition: A prodrug is an inactive compound that the body metabolizes into an active drug [1.3.3].
Purpose: Prodrugs are designed to improve properties like absorption, stability, and site-specific delivery, or to reduce side effects [1.3.4].
Activation: Conversion to the active form typically occurs via enzymatic reactions in the liver, blood, or target tissues [1.3.3].
Active Drugs: In contrast, active drugs are effective immediately upon administration without needing metabolic conversion [1.8.4].
Key Distinction: To identify a drug that is NOT a prodrug, look for one that is administered in its final, active form.
Common Non-Prodrug: Lisinopril is a well-known ACE inhibitor that is an active drug, unlike many others in its class like enalapril [1.11.1].
Common Prodrugs: Famous examples of prodrugs include codeine (becomes morphine) and prednisone (becomes prednisolone) [1.4.5].

What is a Prodrug?

A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug [1.3.3]. In simple terms, prodrugs are inactive or have very low activity when taken and only become effective once the body's enzymes or chemical processes alter their structure [1.3.2]. The inactive portion of the prodrug is often called the 'promoiety' [1.3.1].

This intentional design strategy is used to overcome various challenges in drug development [1.3.4]. For instance, a drug in its active form might have poor absorption, a bad taste, a short half-life, or cause irritation at the injection site [1.8.1, 1.6.1]. By converting it into a prodrug, these properties can be temporarily masked or improved.

The Mechanism: How Prodrugs Become Active

Activation is the critical step that distinguishes a prodrug. This conversion can happen through several mechanisms, but it's typically mediated by common enzymes in the body [1.3.3].

Enzymatic Hydrolysis: Many prodrugs are esters, and enzymes called esterases—found in the liver, blood, and gastrointestinal tract—cleave the ester bond to release the active drug [1.8.1].
Oxidation/Reduction: Cytochrome P450 (CYP450) enzymes in the liver are responsible for many oxidative reactions that can activate prodrugs [1.7.1].

Prodrugs are broadly classified into two main types based on their activation site [1.7.2]:

Type I Prodrugs: Activated inside cells (intracellularly). These can be further divided into Type IA (activation at the therapeutic target cells, e.g., antiviral nucleoside analogs) and Type IB (activation in metabolic tissues like the liver, e.g., carbamazepine) [1.4.2].
Type II Prodrugs: Activated outside cells (extracellularly), such as in digestive fluids or the bloodstream. Examples include loperamide oxide (in GI fluids) and fosphenytoin (in systemic circulation) [1.4.2].

Advantages of the Prodrug Strategy

Designing a drug as a prodrug offers numerous benefits that can enhance its therapeutic efficacy and safety [1.6.5]:

Improved Bioavailability: One of the most common reasons is to enhance absorption. For example, converting a hydrophilic (water-loving) drug into a more lipophilic (fat-loving) prodrug can help it pass through cell membranes in the gut more easily [1.6.5]. Enalapril is a prodrug that is better absorbed than its active form, enalaprilat [1.4.5].
Site-Specific Delivery: Some prodrugs are designed to be activated only at the target site of action, which can reduce systemic side effects. This is a common strategy in cancer therapy [1.6.2].
Enhanced Stability: A drug might be chemically unstable in the acidic environment of the stomach. A prodrug formulation can protect it until it reaches a more favorable environment for absorption [1.6.1].
Reduced Side Effects: By masking the active drug, prodrugs can minimize issues like gastrointestinal irritation or pain upon injection [1.6.1]. Aspirin itself is a prodrug of salicylic acid, which helps reduce gastric irritation compared to taking salicylic acid directly [1.9.1].
Improved Patient Compliance: Prodrugs can be used to mask an unpleasant taste or odor, making the medication more palatable [1.6.1].

Answering: 'Which of the following is not a pro drug?'

To answer this question, you need to distinguish between prodrugs and drugs that are already in their active form when administered. An active drug does not require metabolic conversion to exert its therapeutic effect [1.8.4]. Most medications on the market are active drugs.

Here are some common examples to help you differentiate:

Common Examples of PRODRUGS

Codeine: Metabolized into the active pain reliever, morphine [1.4.5].
Enalapril: An ACE inhibitor that is hydrolyzed to its active form, enalaprilat [1.4.5].
Levodopa (L-DOPA): Crosses the blood-brain barrier and is then converted to dopamine to treat Parkinson's disease [1.8.3].
Clopidogrel (Plavix): An antiplatelet agent that requires activation by liver enzymes [1.4.5].
Prednisone: A corticosteroid that is converted to its active form, prednisolone [1.4.5].
Aspirin: While having its own antiplatelet effect, it is also a prodrug for the anti-inflammatory and analgesic agent, salicylic acid [1.9.1].

Common Examples of Drugs that are NOT Prodrugs (Active Drugs)

Lisinopril: Unlike most other ACE inhibitors, lisinopril is an active drug and does not require metabolism to be effective [1.11.1, 1.11.3]. This is a very common correct answer choice in pharmacology questions.
Morphine: This is the active metabolite of codeine. When administered directly, it is already in its active form and is not a prodrug [1.5.2].
Metformin: A first-line treatment for type 2 diabetes that is administered in its active form [1.10.1]. Although prodrug versions of metformin have been designed to improve absorption, the standard drug itself is not a prodrug [1.10.2].
Ibuprofen: A common NSAID that is active upon administration [1.5.5].
Captopril: Another ACE inhibitor that, like lisinopril, is not a prodrug [1.5.1].

Comparison Table: Prodrug vs. Active Drug


Feature	Prodrug	Active Drug
Form at Administration	Pharmacologically inactive or has low activity [1.3.3].	Pharmacologically active [1.8.4].
Activation Requirement	Must undergo metabolic conversion (enzymatic or chemical) in the body to become active [1.3.2].	No conversion needed to produce a therapeutic effect [1.5.5].
Onset of Action	Generally slower, as it depends on the rate of conversion.	Generally faster, as it is already active.
Purpose of Design	To improve solubility, absorption, stability, site-specificity, or reduce side effects [1.3.4].	The inherent properties of the molecule are suitable for administration.
Example (ACE Inhibitors)	Enalapril (converted to enalaprilat) [1.4.5].	Lisinopril, Captopril [1.5.1].
Example (Opioids)	Codeine (converted to morphine) [1.4.5].	Morphine [1.5.2].

Conclusion

Understanding the distinction between a prodrug and an active drug is a fundamental concept in pharmacology. A prodrug is a clever chemical trick used to improve a medication's performance, requiring the body to 'unlock' its active form. An active drug works right out of the box. So, when faced with the question, 'Which of the following is not a pro drug?', look for the compound that is already in its final, therapeutically effective form. Among ACE inhibitors, lisinopril and captopril are classic examples of active drugs, making them frequent correct answers [1.5.1].

For further reading, you may find this resource helpful: Prodrugs: design and clinical applications | Nature Reviews Drug Discovery

Frequently Asked Questions

A prodrug is an inactive medication that needs to be changed by your body into an active form before it can work. Think of it as a medication that needs to be 'unlocked' by your body's metabolism [1.3.3].

Companies design prodrugs to overcome problems with the active drug, such as poor absorption from the gut, bad taste, chemical instability, or to reduce side effects by targeting the drug to a specific area in the body [1.6.2, 1.6.5].

Yes, aspirin is considered a prodrug. While aspirin itself has an irreversible antiplatelet effect, it is also converted in the body to salicylic acid, which is responsible for most of its anti-inflammatory and analgesic effects [1.9.1].

Lisinopril and captopril are two ACE inhibitors that are not prodrugs. They are administered in their active form and do not require hepatic (liver) metabolism to become effective, unlike other ACE inhibitors such as enalapril or ramipril [1.5.1].

No, morphine is not a prodrug. It is an active opioid analgesic. In fact, it is the active metabolite of the prodrug codeine [1.5.2, 1.4.5].

The two main types are Type I, which are activated inside cells (intracellularly), and Type II, which are activated outside cells (extracellularly), for example in the blood or digestive fluids [1.7.2].

No, the commonly prescribed medication Metformin is not a prodrug; it is administered in its active form. Researchers have, however, designed experimental prodrug versions of metformin to try to improve its absorption and reduce side effects [1.10.1, 1.10.2].