Pharmacokinetics I: Key Concepts and Principles

Pharmacokinetics

Movement and modification of medications in the body.

Absorption

Transfer of medication from site of administration into circulation.

Distribution

Process by which drug reversibly leaves bloodstream and enters extracellular fluids and tissues.

Metabolism

Process by which body chemically modifies drugs to allow drug to be eliminated from body more easily.

Prodrug

Inactive precursor chemical that is absorbed and then converted to active drug.

Bioavailability

The relevance of a drug's absorption in terms of the proportion of the drug that enters circulation when introduced into the body.

Apparent volume of distribution

A pharmacokinetic parameter that describes the distribution of a drug within the body.

Routes of administration

Different methods by which drugs can be delivered into the body, each with distinct characteristics.

Factors affecting drug absorption

Various elements that influence the rate and extent to which a drug is absorbed into the bloodstream.

Factors affecting drug distribution

Elements that influence how a drug is distributed throughout the body's tissues and fluids.

PK Parameters

Four pharmacokinetic principles: Absorption, Distribution, Metabolism, and Elimination.

Elimination

The process by which drugs are removed from the body.

Drug transformation

The process that occurs from absorption to elimination of the drug.

Site of action

The specific location in the body where a drug exerts its therapeutic effect.

Extracellular fluids

The body fluids outside of cells where drugs can distribute.

Characteristics of each route of administration

Distinctive features and implications of each method used to administer drugs.

Clinical significance of pharmacokinetics

The importance of understanding pharmacokinetics in the context of drug therapy and patient care.

Excretion

Process by which drugs or their metabolites are eliminated from the body.

ADME

Affects different drug factors including Onset, Intensity, and Duration.

Drug Regimens

Used to design appropriate drug regimens.

Route of Administration

The method by which a drug is delivered to the body.

Dose

The amount of drug administered.

Frequency

How often a drug is administered.

Length of Treatment

Duration for which a drug is administered.

Enteral Administration

Administration through the mouth.

Types of Enteral Administration

Includes Oral (PO), Sublingual (SL), and Buccal.

Oral (PO)

Convenient, easy administration but has disadvantages including pathways involved with drug absorption.

Sublingual/Buccal

Rapid absorption directly into the bloodstream, bypassing GI and avoiding first pass metabolism.

Parenteral Administration

Drug introduced directly into systemic circulation.

Advantages of Parenteral Administration

Rapid onset of action and dosing control.

Disadvantages of Parenteral Administration

Local tissue damage/infections.

Types of Parenteral Administration

Includes Intramuscular (IM), Subcutaneous (SC), Intravenous (IV), and Intradermal (ID).

Inhalation/Nasal Preps

Rapid delivery of drug with effects almost as rapid as with IV bolus.

Intrathecal/Intraventricular

Directly into the CSF for local, rapid effects.

Topical Administration

Used for local effect.

Transdermal Administration

Systemic effects with slower absorption and prolonged duration of action.

Rectal Administration

Bypasses ~50% of portal circulation, minimizing biotransformation of drugs by liver.

Absorption

Transfer of medication from site of administration into bloodstream.

Bioavailability

Percent of medication reaching circulation.

Passive Diffusion

Movement of drugs across membranes without energy, following concentration gradient.

Facilitated Diffusion

Transmembrane carrier proteins undergo conformational changes to transport large molecules without energy.

Active Transport

Energy dependent movement of drugs across a concentration gradient.

Endocytosis

Process of taking large drugs into the cell.

Exocytosis

Process of expelling large drugs out of the cell.

Factors Influencing Absorption

Includes physicochemical properties of drug, pH, blood flow, total surface area, contact time, and expression of P-glycoprotein.

pKa

Measure of strength of interaction between compound and a proton.

Bioavailability Calculation

F = mass of drug delivered to plasma ÷ total mass of drug administered.

Oral Bioavailability

The oral bioavailability (F) of a drug is 50%.

Excretion

Process by which drugs or their metabolites are eliminated from the body

ADME

Affects different drug factors including Onset, Intensity, and Duration

Drug Regimens

Used to design appropriate drug regimens

Route of Administration

The method by which a drug is delivered to the body

Dose

The amount of drug administered

Frequency

How often a drug is administered

Length of Treatment

Duration for which a drug is administered

Enteral Administration

Administration through the mouth

Types of Enteral Administration

Includes Oral (PO), Sublingual (SL), and Buccal

Oral (PO)

Convenient, easy administration; disadvantages include pathways involved with drug absorption

Sublingual/Buccal

Rapid absorption directly into bloodstream, bypasses GI, avoids first pass metabolism

Parenteral Administration

Drug introduced directly into systemic circulation

Advantages of Parenteral Administration

Rapid onset of action and dosing control

Disadvantages of Parenteral Administration

Local tissue damage/infections

Types of Parenteral Administration

Includes Intramuscular (IM), Subcutaneous (SC), Intravenous (IV), and Intradermal (ID)

Inhalation/Nasal Preparations

Rapid delivery of drug; effects almost as rapid as with IV bolus

Intrathecal/Intraventricular

Directly into the CSF for local, rapid effects

Topical Administration

Used for local effect

Transdermal Administration

Systemic effects with slower absorption and prolonged duration of action

Rectal Administration

Bypasses ~50% of portal circulation, minimizing biotransformation of drugs by liver

Absorption

Transfer of medication from site of administration into bloodstream

Bioavailability

Percent of medication reaching circulation

Passive Diffusion

Movement of drugs across membranes without energy, not saturable

Facilitated Diffusion

Involves transmembrane carrier proteins, faster than passive diffusion, does not require energy

Active Transport

Energy dependent movement of drugs across a concentration gradient

Endocytosis

Process of taking large drugs into the cell

Exocytosis

Process of expelling large drugs out of the cell

Factors Influencing Absorption

Includes physicochemical properties of drug, pH, blood flow, total surface area, contact time, and expression of P-glycoprotein

pKa

Measure of strength of interaction between compound and a proton

Bioavailability Calculation

F = mass of drug delivered to plasma ÷ total mass of drug administered

Calculating Bioavailability

If oral bioavailability (F) of a drug is 50% and standard IV dose is 50mg, the appropriate oral dose would be calculated accordingly.

Bioavailability

F= mass of drug delivered to plasma ÷ total mass of drug administered

First-pass metabolism

PO drugs pass through GIT and portal circulation before reaching systemic circulation

Metabolism

Metabolism in liver and gut wall

Solubility of the drug

Very hydrophilic meds poorly absorbed- lipid rich cell membranes

Chemical instability

Instability in stomach pH and GI tract enzymes

Nature of drug formulation

Drug formulation effects dissolution and rate of absorption

Drug Distribution

Process by which drug reversibly leaves bloodstream and enters extracellular fluids and tissues

Distribution factors

Cardiac output and local blood flow, capillary permeability, binding of drugs to plasma proteins and tissues, lipophilicity, volume of distribution

Blood flow

The greater the blood flow to tissues, the greater the distribution

Capillary structure

Determined by capillary structure & chemical nature of drug

Slit junctions

Allow delivery of large protein-bound molecules

Tight junctions

Prevent large, protein-bound and hydrophilic drugs from easily passing through; form barrier

Blood-brain barrier (BBB)

Capillary structure continuous with tight junctions that form a barrier preventing certain drugs from entering the brain

Lipid soluble drugs

Readily penetrate CNS

Ionized or polar drugs

Cannot enter CNS

Plasma proteins

Albumin- major drug binding protein

Tissue proteins

Drugs tend to accumulate in tissues, serving as a source of drug

Apparent Volume of Distribution

Vd= Amount of drug in body ÷ Plasma drug concentration (C)

Theoretical volume of distribution

Based on relationship between total amount of drug administered and measured concentration in plasma

Chloroquine

Apparent volume of distribution = 13,000L/70kg patient

Digoxin

Apparent volume of distribution = 500L/70kg patient