Pharmacokinetics

 Pharmacokinetics (PK) is a fundamental branch of pharmacology that describes what the body does to a drug after administration. It focuses on the movement of drugs within the body, tracking how a drug is absorbed, distributed, metabolized, and excreted commonly known as the ADME process.

Understanding pharmacokinetics is essential for determining appropriate dosing, frequency, and duration of therapy to achieve optimal therapeutic effects while minimizing toxicity.

Definition

Pharmacokinetics refers to the quantitative study of the time course of drugs within the body. It involves mathematical models to describe the rates at which a drug moves between compartments in the body and is eventually eliminated.

Pharmacokinetics = What the body does to the drug

Pharmacokinetic Processes (ADME)

The four primary processes of pharmacokinetics are:

1. Absorption

2. Distribution

3. Metabolism (Biotransformation)

4. Excretion

Pharmacokinetic Processes (ADME)

The four primary processes of pharmacokinetics are:

1. Absorption

2. Distribution

3. Metabolism (Biotransformation)

4. Excretion

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1. Absorption

Definition:
Absorption is the process by which a drug moves from its site of administration into the systemic circulation (bloodstream).

Key Routes of Administration:

• Oral (PO) – most common

• Intravenous (IV) – direct into the bloodstream

• Intramuscular (IM)

• Subcutaneous (SC)

• Sublingual

• Rectal

• Transdermal

• Inhalational

Factors Affecting Absorption:

• Drug solubility and formulation

• pH and pKa of the drug

• Gastrointestinal (GI) motility

• Presence of food in the stomach

• Blood flow to absorption site

• Surface area of absorption

Bioavailability (F):

• It is the fraction of an administered dose that reaches systemic circulation in its active form.

• For IV administration, bioavailability is 100%.

• Oral administration often results in reduced bioavailability due to first-pass metabolism.

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2. Distribution

Definition:
Distribution is the process by which the drug is dispersed throughout the body fluids and tissues after entering the bloodstream.

Key Determinants of Distribution:

• Blood flow to tissues

• Plasma protein binding (e.g., albumin)

• Lipid solubility of the drug

• Capillary permeability

• Tissue binding

Volume of Distribution (Vd):

• A theoretical volume that relates the amount of drug in the body to the plasma concentration.

• Higher Vd indicates greater distribution into tissues.

$$Vd = \frac{\text{Total amount of drug in the body}}{\text{Plasma drug concentration}}$$

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3. Metabolism (Biotransformation)

Definition:
Metabolism refers to the chemical alteration of the drug in the body, mainly by liver enzymes, converting it into more water-soluble metabolites for easier excretion.

Phases of Metabolism:

• Phase I: Modification reactions (oxidation, reduction, hydrolysis)

  • Mainly via the Cytochrome P450 (CYP450) enzyme system

  • Results in activation, inactivation, or conversion to toxic metabolites

• Phase II: Conjugation reactions (glucuronidation, sulfation, acetylation)

  • Makes metabolites more water-soluble

First-Pass Effect:

• Drugs absorbed via the GI tract first pass through the liver via the portal vein, where they may be metabolized before reaching systemic circulation.

• This reduces the effective concentration of the drug.

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4. Excretion

Definition:
Excretion is the process of removing drugs and their metabolites from the body.

Primary Routes of Excretion:

• Renal (urine) – major route

• Biliary (feces)

• Lungs (volatile substances)

• Sweat, saliva, breast milk

Renal Excretion Processes:

1. Glomerular Filtration

2. Tubular Secretion

3. Tubular Reabsorption

Clearance (Cl):

• The volume of plasma from which a drug is completely removed per unit time.

$$Cl = \frac{\text{Rate of elimination}}{\text{Plasma drug concentration}}$$

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Pharmacokinetic Parameters

1. Half-life (t1/2):

   • Time required for the plasma concentration of a drug to reduce by half.

   • Indicates how long a drug stays in the body.

2. Area Under the Curve (AUC):

   • Represents the total drug exposure over time.

3. Cmax and Tmax:

   • Cmax: Maximum plasma concentration achieved.

   • Tmax: Time taken to reach Cmax.

4. Bioavailability (F):

   • Percentage of the administered drug reaching systemic circulation.

5. Steady-State Concentration (Css):

   • Achieved when the rate of drug administration equals the rate of elimination.

6. Therapeutic Window:

   • The concentration range where the drug is effective without being toxic.

Below Flow Chart For How to work Pharmacokinetics process

Factors Influencing Pharmacokinetics

1. Age

   • Neonates and elderly may have reduced metabolism and excretion.

2. Genetics

   • Variations in metabolic enzymes (pharmacogenomics)

3. Body Composition

   • Fat content, body water affect distribution.

4. Disease States

   • Liver and kidney dysfunction impact metabolism and excretion.

5. Drug Interactions

   • Some drugs induce or inhibit enzymes affecting metabolism.

6. Diet and Lifestyle

   • Food, alcohol, smoking can influence drug metabolism.

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Clinical Significance of Pharmacokinetics

• Dose Calculation: Determines correct dose and interval.

• Therapeutic Drug Monitoring: Ensures plasma levels stay within therapeutic range.

• Understanding Drug Interactions: Predicts effects when combining drugs.

• Individualized Therapy: Adjust dosing in liver/kidney impairment.

• Bioequivalence Studies: For generic drug approval.

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Mathematical Models in Pharmacokinetics

1. One-Compartment Model: Assumes body acts as a single uniform compartment.

2. Two-Compartment Model: Divides body into central (blood and organs) and peripheral (tissues) compartments.

3. Non-Compartmental Analysis: Uses statistical models without assuming compartments.

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Applications in Drug Development

• Determines optimal drug formulation.

• Predicts behavior of new drugs.

• Assists in the design of controlled-release formulations.

• Establishes dosing in special populations (e.g., children, elderly).

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Conclusion

Pharmacokinetics is an essential aspect of clinical pharmacology and therapeutics. Understanding how drugs are absorbed, distributed, metabolized, and excreted enables healthcare providers to design safe and effective treatment regimens tailored to individual patient needs.

By integrating pharmacokinetic principles with pharmacodynamics, clinicians can maximize therapeutic efficacy, minimize toxicity, and achieve personalized medicine.