Pharmakokinetics Flashcards
Definition of Pharmacokinetics
what the body does to the drug
Definition of pharmacodynamics
what the drug does to the body
PK/PD definition
relation between pharmacokinetic and pharmacodynamic
what are the 2 primary measures
- CLEARANCE
- VOLUME OF DISTRIBUTION
clearance is the only parameter that determines what?
Clearance (Cl) is the only parameter that determines maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at stetheady state
what is volume of distribution
Volume of distribution (Vd) is an essential determinant of drug half-life, as t1/2 = 0.693 * Vd/Cl.
What this means is that for 2 drugs with the same clearance, but different voluymes of distribution, the bigger volume with have a longer half-life.
what is bioavailability
Fraction of unchanged drug reaching the systemic circulation (F).
what does systemic circulation (F) depend on in intravenous dosing?
f = 100%
what does systemic circulation (F) depend on in oral dosing?
F depends on Absorption and Clearance
what are 2 types of in vivo PK experiments
IV bolus dose
oral dose
where is an intravenous bolus administered
plasma compartment
where is oral dosing administered
Dosed into the gastro-intestinal tract
what is Absorption
The Process by which a drug moves from the site of administration to the site of action
what is absorption quantified by
Quantified by the Absorption rate constant (A First Order Process)
what 3 unique properties does oral absorption require
Water Soluble in the gut
Lipophilic for membrane permeation
Water soluble in plasma
what is distribution
is the process by which a drug moves from the bloodstream into the peripheral tissues
what is distribution driven by
Driven by the relative affinity of binding for blood and tissue compartments
what is distribution quantified by
Quantified by the Volume of Distribution (Vd)
“The ratio between the amount of drug in the body and the amount in the plasma”
what 2 ways can calculate volume of distribution
metabolism definition
Metabolism is the irreversible chemical alteration of a drug by a biological system
Drug Metabolism can happen in most organs and is covered by 2 Phases:
what are the 3 phase 1 reactions and what is its aim
Introduces a new chemical group via:
Oxidation Reactions
Reduction Reactions
Hydrolysis Reactions
Aim: To produce Inactive metabolites
Drug Metabolism can happen in most organs and is covered by 2 Phases:
what are the 3 phase 2 reactions and what is its aim
Conjugates the molecule with charged chemical species via:
Glucouronidation
Acylation
Sulfation
Aim: To decrease lipophilicity and increase solubility for enhanced excretion
what is excretion
Excretion is the irreversible elimination of a drug from the systemic circulation and Clearance can be used to define excretion
what are the 2 routes that make up drug excretion
Renal Excretion – Into the Urine
Hepatic Excretion – Into the Bile (Faeces)
what are 3 other excretion routes
Sweat
Milk
Saliva
what is half life
Half life (t1/2): This is the time taken for the plasma concentration of a drug to decline by 50%
what are the two phases of metabolism?
Phase 1 → drug is inactivated
Phase 2 → making drug more susceptible for elimination
what must we do to out curve before calculating the elimination rate constant (k)?
what must we do to out curve before calculating the elimination rate constant (k)?
how do we calculate the half life of a drug?
On a first order monoexponential decline curve, the half-life can be estimated anywhere on the curve
the slope of the line in a galf life graph is equal to what
Slope of the line = Elimination rate constant (k)
what 2 ways lets you calculate the slope of the line
what is the most important primary measure of PK
Clearance is the most Important Primary Measure of PK
what effect does low clearance have on the theraputic effect
Why is Clearance important?
Clearance is the ONLY parameter that determines the maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at steady state
what are 2 ways of calculating total clearance
what is the main organ for drug clearance
liver
What affects the hepatic clearance?
Enzymatic activity in the liver
Hepatic blood flow (Rate Limiting Step
what is maximum hepatic clearance equal to?
Maximum hepatic clearance is equal to liver blood flow (Q)
Therefore, if the total blood clearance is greater than liver blood flow (Q), there must be extra-hepatic clearance
how do we calculate hepatic clearance?
Hepatic clearance = liver blood flow X Extraction ratio
what 2 things determines the clearance by each organ
Extraction ratio and Blood flow for each organ determines the clearance by each organ
what is whole body clearance
Whole body clearance is the sum of all organ clearances
What is the bioavailability of a drug?
fraction of unchanged drug that reaches the systemic circulation
for IV dosing, f must equal what
F must always equal 1 (100%)
For Oral Dosing, Bioavailability depends on what 2 things:
Absorption from the Gut
Clearance
Bioavailability is calculated using dose-adjusted AUCs of oral and iv dosing by:
Why can a drug be 100% absorbed but still have zero bioavailability?
first pass effect
*key equation to remember
Relationship between half-life (t1/2) in hours and the elimination rate constant (k) (hours-1)
t1/2 = 0.693 / k
*key equation to remember
Volume of distribution (Vd, Units: mL, L)
𝑉𝑑=𝐷𝑜𝑠𝑒 𝐴/𝐴0
*key equation to remember
Whole Body Clearance (Cl, Units: mL.min-1, L.h-1)
𝐶𝐿=𝑘 ∗𝑉𝑑
𝐶𝑙=𝑑𝑜𝑠𝑒 ∗𝐹 /𝐴𝑈𝐶
*key equation to remember
Oral Bioavailability (F, Units: %)
describe where the following would be on a pharmacokinetics graph:
safety window
toxicity level
minimum effective concentration
theraputic window
