Drug Potency

Understanding Drug Potency, Efficacy, and Affinity

• The mathematical model uses the median effective concentration/dose KD, EC50, or ED50 to denote potency.
• Potency is the drug range over which a response is produced, while efficacy is the ability to produce a response once the drug binds the receptor.
• Affinity is the strength with which a drug binds to a receptor and is inversely proportional to potency.
• Drug A shows 100% response with a potency of 300 mg, while Drug B shows a 20% response with the same potency, and Drug C shows a 40% response with a potency of 10 mg.
• Antagonist drugs, like naloxone, have high affinity but zero efficacy, while agonist drugs, like morphine, activate the receptor and produce a biochemical activity.
• Some treatments are administered in combination for synergism, where two treatments with similar effects produce greater efficacy together.
• Receptors are macromolecules located on cells, and the molecules that bind to them are called ligands.
• Affinity is how avidly a drug binds its receptor, while efficacy is the drug's ability to activate the receptor once it has bound to it.
• Affinity and efficacy are different concepts, and a higher potency does not necessarily mean higher efficacy.
• Potency is the measure of the necessary amount of drug to produce an effect of a given magnitude and is affected by its affinity.
• Drugs work by binding to specific receptors and activating them, causing a downstream effect.
• Affinity is like a drug's desire to connect to an open receptor, while potency is how powerful or strong a drug is.

Phases of Clinical Trials: From Preclinical to Human Studies

• Preclinical studies involve in vitro and in vivo experiments to determine preliminary efficacy, toxicity, and pharmacokinetic information of a study agent
• Phase 0 trials, known as human microdosing studies, involve administering subtherapeutic doses to a small number of subjects to gather preliminary pharmacokinetic data
• Phase 0 trials do not provide safety or efficacy data and are used to rank drug candidates for further development based on human models
• Phase I trials are the first stage of testing in human subjects, focusing on safety, side effects, best dose, and formulation method for the drug
• Phase I trials typically involve 20-100 healthy volunteers and are often conducted in clinical trial clinics by contract research organizations
• These trials assess safety, tolerability, pharmacokinetics, and pharmacodynamics of a drug, often including dose-ranging studies to find the safest dose
• Phase I trials may include healthy volunteers or clinical patients, such as those with terminal cancer or HIV, and are conducted in tightly controlled clinics
• Volunteers in Phase I trials are paid a variable inconvenience fee for their time spent in the volunteer center
• Phase I trials can be further divided into Phase Ia (single ascending dose) and Phase Ib (multiple ascending dose) studies, each with specific objectives and designs
• Phase Ia studies involve giving a single dose of the drug to small groups of subjects and escalating the dose based on safety and pharmacokinetic data
• Phase Ib studies investigate the pharmacokinetics and pharmacodynamics of multiple doses of the drug, looking at safety and tolerability
• Food effect studies are short trials designed to investigate any differences in drug absorption caused by eating before the drug is given, often conducted as crossover studies.

Phases of Clinical Trials: From Preclinical to Human Studies

• Preclinical studies involve in vitro and in vivo experiments to determine preliminary efficacy, toxicity, and pharmacokinetic information of a study agent
• Phase 0 trials, known as human microdosing studies, involve administering subtherapeutic doses to a small number of subjects to gather preliminary pharmacokinetic data
• Phase 0 trials do not provide safety or efficacy data and are used to rank drug candidates for further development based on human models
• Phase I trials are the first stage of testing in human subjects, focusing on safety, side effects, best dose, and formulation method for the drug
• Phase I trials typically involve 20-100 healthy volunteers and are often conducted in clinical trial clinics by contract research organizations
• These trials assess safety, tolerability, pharmacokinetics, and pharmacodynamics of a drug, often including dose-ranging studies to find the safest dose
• Phase I trials may include healthy volunteers or clinical patients, such as those with terminal cancer or HIV, and are conducted in tightly controlled clinics
• Volunteers in Phase I trials are paid a variable inconvenience fee for their time spent in the volunteer center
• Phase I trials can be further divided into Phase Ia (single ascending dose) and Phase Ib (multiple ascending dose) studies, each with specific objectives and designs
• Phase Ia studies involve giving a single dose of the drug to small groups of subjects and escalating the dose based on safety and pharmacokinetic data
• Phase Ib studies investigate the pharmacokinetics and pharmacodynamics of multiple doses of the drug, looking at safety and tolerability
• Food effect studies are short trials designed to investigate any differences in drug absorption caused by eating before the drug is given, often conducted as crossover studies.