test 3 Flashcards
Bioavailability
Rate and extent to which the active ingredient is absorbed from drug product and becomes available at the site of action
What is bioavailability influenced by?
Method of manufacture
Particle size
Crystal form
Properties of excipients
Physical changes as drug products age
What do BA studies used to compare?
Different dosage forms via different routes (which one has the most desirable absorption pattern)
What are BA studies used to estimate?
Administration dose that gets into circulation
The effect of food on the drug
Distribution and elimination characteristics
Performance of the formulation
Bioequivalence
Absence of bioavailability difference between the test drug and reference drug
What is plasma concentration used for in be testing?
It is considered a surrogate for the concentration of the drug at the site of action
What are BE studies used for?
To compare the BAs of different formulations, drug products or batches of the same drug
How do you find the relative bioavailability?
Dose of ref product x AUC of test drug after oral admin/ Dose of test drug x AUC of reference drug after oral dose
What is relative bioavailability used to see?
Drug drug interactions
Food effects
How new formulations impact bioavailability
What are cross over design studies used for?
For determination of therapeutic equivalence between generic and reference drug
What does AUC represent?
The total amount of drug absorbed into circulation
Compare total exposure or extent of drug absorption
How do you find absolute bioavailability?
IV dose x AUC after oral dose/
Oral dose x AUC after IV dose
What are therapeutic equivalents?
Drug products that are pharmaceutical equivalents with the same clinical effect and safety profile for which bioequivalence has been demonstrated
What are pharmaceutical equivalents?
Drug products that have identical dose of identical API with the same esters or salt forms and identical dosage forms
What are pharamaceutical alternatives?
Identical API or precursor that do not have the same amount, dosage forms, or salt or ester
What is class one of BCS classes?
High solubility and high permeability
What is class 2 of BCS?
Low solubility and high permeability
What is class 3 of BCS?
High solubility and low permeability
What is class 4 of BCS?
Low solubility and low permeability?
What classes do not require BABE studies?
Class 1 and 3 (high permeability)
What is the Orange Book?
A book of approved drug products with therapeutic equivalence evaluations
According to the Arrhenius equation, what happens when temperature increases?
The rate of the reaction does as well
What is shelf life?
Time interval that a drug product is expected to remain within the approved shelf life under specific conditions (90% of the drug left)
What is shelf life used for?
Used to determine expiration date of drug products
What are the different methods to determine shelf life?
Direct Methods
Predictive Models Development
Accelerated shelf life studies
What is the direct method to determine shelf life?
Storing product under specific conditions for a longer period of time and seeing when it begins to degrade
What is the predictive models development?
Uses data from a database to calculate shelf life
What is the accelerated shelf life studies?
Study it for 6 months
Deliberately increase the rate of degredation by increasing the temperature and humidity
How do you find the shelf life from changing the temperature?
Original shelf life/
Q10^(T2-T1)/10
What is Q10?
Temperature coefficient
Factor by which the rate of drug degradation increases when the temp is raised by 10 degrees celcius
What does Q10 allow for?
Allows for the prediction of a drug products shelf life under real life conditions
When do you use the linear traqezoidal method?
when plasma concentration is increasing (absorption)
When do you use the log trapezoidal method?
When plasma concentration is decreasing (elimination phase)
What does the one compartment model assume?
That the body is a single uniform compartment
Instantaneous dose
Rapid distribution
Drug elimination starts immediately upon admin
What is the well stirred model?
Uniform and instantaneous distribution model
What is the volume of distribution?
Not an actual volume just a theoretical volume in which drug distributes throughout the body
How do you get K?
elimination rate/amount in body
How do you get Co?
Dose/ Vd
What is k?
The elimination rate constant
What does k tell us?
The proportion of the rate of drug elimination and the amount of drug in the body at any given time
What does the 1 com model predict?
Predicts concentration in plasma not the tissues (plasma concentration should be eliminated at the same rate as tissue)
How do you get half life?
0.693/k
How do you get k from slope?
lny2-lny1/t2-t1
How do you get clearance?
Vdk
What is clearance?
Volume of plasma fluid cleared of drug per unit of time.
What is Pk?
Study of dependence of physiological process and response of the drug
What is drug stability?
The time dependent degradation of a drug product
Why do we use straight lines for relationships?
To interpret the data and create rates
