What do you mean by drug bioavailability ? Elaborate the procedure for developing a newer drug.

What is Drug Bioavailability?

Drug bioavailability (F) is a fraction, expressed as a percentage or decimal, representing the extent and rate at which the active drug substance is absorbed from its dosage form and becomes available at the site of action. A drug may be chemically and physiologically active, but if it cannot reach its target site in sufficient concentration, it will be ineffective. Several factors influence bioavailability, including drug formulation, route of administration, physiological factors (e.g., gastric pH, intestinal motility), and first-pass metabolism.

For example, intravenous administration has a bioavailability of 100% because the drug is directly introduced into the bloodstream. Oral drugs, however, often have lower bioavailability due to incomplete absorption and extensive first-pass metabolism in the liver.

Procedure for Developing a Newer Drug

The drug development process is broadly divided into several phases, each with specific objectives and regulatory requirements. The process is highly regulated by agencies like the US FDA (Food and Drug Administration) and the CDSCO (Central Drugs Standard Control Organization) in India.

1. Target Identification and Validation

This initial phase involves identifying a disease or condition where a new drug is needed and validating a specific biological target (e.g., a protein or enzyme) that plays a crucial role in the disease process. This stage often involves extensive basic research.

2. Drug Discovery and Lead Identification

Once a target is validated, researchers screen thousands of compounds (natural products, synthetic chemicals, or existing drugs) to identify "lead" compounds that interact with the target and have a desired effect. High-throughput screening (HTS) is commonly employed. Computational chemistry and structure-based drug design are also used.

3. Preclinical Development

Lead compounds undergo preclinical testing, which includes in vitro (laboratory studies) and in vivo (animal studies). These studies evaluate the drug's safety, efficacy, and pharmacokinetic properties (absorption, distribution, metabolism, and excretion - ADME). Bioavailability is a critical parameter assessed during this phase.

Example: The development of Remdesivir, an antiviral drug used to treat COVID-19, involved extensive preclinical studies to assess its efficacy against SARS-CoV-2 in cell cultures and animal models before human trials.

4. Clinical Development (Human Trials)

If preclinical studies are promising, the drug candidate enters clinical trials, which are conducted in three phases:

• Phase 1: Small group of healthy volunteers (20-80). Focuses on safety and dosage.
• Phase 2: Larger group of patients with the target disease (100-300). Assesses efficacy and side effects.
• Phase 3: Large, randomized controlled trials (RCTs) involving hundreds or thousands of patients. Confirms efficacy, monitors adverse reactions, and compares the drug to existing treatments.

5. Regulatory Review and Approval

After successful completion of Phase 3 trials, the pharmaceutical company submits a New Drug Application (NDA) (in the US) or equivalent application to the regulatory agency. The agency reviews the data to assess the drug's safety and efficacy.

Statistic: The average cost of developing a new drug is estimated to be between $1.3 billion and $2.6 billion (DiMasi et al., 2018). This includes the cost of failures.

6. Post-Market Surveillance (Phase 4)

Even after approval, the drug is monitored for long-term effects and rare adverse events. This phase is crucial for identifying previously unknown risks and optimizing drug use. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or other drug-related problems.

Phase	Objective	Participants	Duration
Phase 1	Safety & Dosage	20-80 Healthy Volunteers	Several Months
Phase 2	Efficacy & Side Effects	100-300 Patients	Several Months to 2 Years
Phase 3	Confirm Efficacy, Monitor Adverse Reactions	Hundreds to Thousands of Patients	1-4 Years

Challenges in Drug Development

• High failure rate – many drug candidates fail during clinical trials.
• Increasing regulatory scrutiny – stricter requirements for safety and efficacy.
• Rising development costs – making it difficult for smaller companies to compete.
• Ethical considerations – ensuring patient safety and informed consent.

Scheme: The Indian government’s “Drugs & Medical Devices Act, 1940” and subsequent amendments govern the manufacturing, sale, and distribution of drugs in India. The Drugs Price Control Order (DPCO) regulates the prices of essential medicines.

Imatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). Its development involved identifying the BCR-ABL fusion gene as a key driver of CML. Extensive preclinical and clinical trials demonstrated its efficacy in suppressing CML cells and significantly improving patient survival. The drug exemplifies targeted therapy and personalized medicine. Imatinib revolutionized the treatment of CML, transforming it from a fatal disease to a manageable chronic condition.