III Flashcards
IV Time to Effect
30-60 seconds
IM Time to effect
10-20 minutes
SC Time to effect
15-30 minutes
Oral Time to effect
30-90 minutes
Sublingual Time to effect
3-5 minutes.
Inhalation time to effect
2-3 minutes
Transdermal time to effect
minutes to hours.
Rectal Time to effect
5-30 minutes
IV dose is limited by the _________ of the drug.
Solubility
Which routes of administration require a trained health professional?
IV and IM injections.
What are the volumes of IM and SQ injections?
3-5 mL (IM)
1-3 mL (SQ)
T or F: The site of an injection will influence the absorption.
True.
Subcutaneous absorption is limited by ________
Blood Flow
Pulmonary route of administration must by pass both ______ clearance and __________ in order to deliver the dose to the alveoli.
- Mucociliary Clearance
- Alveolar Macrophages.
T or F: Drugs absorbed through the sublingual route undergo significant first pass metabolism.
False
The sublingual route of administration is not suitable for what drugs.
Irritant Drugs and Large MW drugs.
Approximately 60% of small molecules drugs are administered via which route?
Oral
What is the pH of saliva, and how long is an orally absorbed drug subject to it?
pH: 6.5-7.5
Time: ~1 minute
What is the pH of the upper stomach? How long is an orally absorbed drug subject to it?
pH: 4.0-6.5
time: 30-60 minutes
What is the pH of the lower stomach? How long is an orally absorbed drug subject to it?
pH: 1.5-4.0
Time: 1-3 hours
What is the pH of the duodenum? How long is an orally absorbed drug subject to it?
pH: 7.0-8.5
Time: 30-60 minutes
What is the pH of the small intestine? How long is an orally absorbed drug subject to it?
pH: 4-7
Time: 1-5 hours
What is the pH of the large intestine? How long is an orally absorbed drug subject to it?
pH: 4-7 hours
Time: 10 hours
Folds of Kerkring
Mucosal Folds of the small intestine.
SA = 10000 cm^2
Villi
Small finger like projections in the small intestine. These increase the surface area available for absorption.
SA= 100,000 cm^2
Microvilli
microscopic cellular protrusions which increase surface area for diffusion. These are found in the small intestine.
SA= 2,000,000 cm^2
Dissolution
Solid drugs must be dissolved before they can be absorbed.
Disintegration
Breakdown of solid drugs into smaller particles.
Passive Transcellular Transport
Transport of solutes without energy. This is bidirectional and occurs along a concentration gradient.
Molecules involved are: Lipophilic and unionized.
Active Transcellular Transport
Carrier Mediated Transport (Transporter). This occurs in a substrate dependent direction.
What are limitations of active transcellular transport?[3]
- Saturable
- Stereo chemically dependent
- Inhibitable
What molecules undergo active transcellular transport primarily?
Hydrophilic molecules.
What is paracellular diffusion?
Bidirectional diffusion along a concentration gradient by passing through the intracellular space between cells.
What are the limitations of paracellular diffusion?
- Low capacity
- Saturable
What molecules undergo paracellular diffusion?
Hydrophilic molecules.
Transcytosis
Receptor mediated endocytosis. This is where macromolecules are captured in vesicles and ejected to the other side of the cell.
What is the direction of transcytosis
Mucosal layer–> serosal layer
What is the driving force of transcytosis?
Active transport
What are the limitations of transcytosis?[3-4]
- Low capacity
- Saturable
- Likely stereo chemically dependent
- Can be inhibited
What molecules undergo transcytosis?
macromolecules.
For most drugs; is dissolution rate faster or slower than absorption rate?
Dissolution rate is either the same or faster than absorption rate.
Is it possible for absorption rate to be faster than dissolution rate?
No, because you cannot absorb the entire drug if it has not been dissolved. Furthermore, slow dissolution is considered to be a rate-limiting factor of absorption.
Immediate Release Definition
85%+ is absorbed within 30 minutes of administration.
Extended Release
Modified Dosage Form which prolongs the time of drug release. (note the time of effect is not delayed.)
Delayed Release
Modified dosage form which delays the time until the drug is released following administration. However, once the drug is released it is absorbed at a similar rate to an immediate release product.
Scientific Discipline that examines the interrelationships of the physiochemical properties of the drug, the dosage form in which the drug is given, and the route of administration on the rate and extent of drug absorption.
Biopharmaceutics
Inventor: Gerhard Levy
Oral absorption of drugs often approximates _____ kinetics.
First Order
First Order Absorption Rate Constant
Ka
First Order Absorption Half-Life
0.693 / Ka
First Order Absorption Rate
Ka * Aa
Aa= Amount remaining to be absorbed.
Compare and Contrast First Order and Zero Order Kinetics
First Order = Concentration Dependent
Zero Order = Concentration Independent.
Zero-Order will go to zero. Where first order will never do this.
Cmax
The peak concentration following administration of a drug.
Tmax
The time at which the peak concentration occurs following the administration of a drug.
How do you calculate the remaining drug to be absorbed?
X= Dose * Bioavailability
What is the Bateman Function and what is its purpose?
(See page 6 of notes)
The bateman function is used to calculate the plasma concentration at any time following a single oral dose.
What are the major PK parameters?
Absorption Parameters(F, Ka)
Disposition Parameters(Cl(Kel), V)
What does the Bateman Function Assume?
First Order Elimination
Ka is normally __________ than Kel
Ka is normally faster than Kel, therefore it is usually presumed that Kel is the rate limiting factor of oral absorption.
Remember, Kel is the elimination rate constant.
The method of residuals works best if:
1)___________
2) ____________
1) Both absorption and elimination are first order processes.
2) One rate constant is at least five times larger than the other. (ka or kel)
What is the slope of a semi-log graph of Cp vs time?
Kel
What is Y-intercept of a semi-log graph of Cp vs time?
Co= Initial Plasma Concentration
How are the residual values calculated in the method of residuals?
Cp(late) - Cp
What is the slope of the residuals graph?
Ka
The Y-intercept should be the same as the Terminal slope graph.
How do we calculate the elimination half-life in the method of residuals?
0.693/Kel
This is assuming kel is less than Ka. Otherwise Ka would be the rate limiting factor in elimination.
How do we calculate the absorption half-life in the method of residuals?
0.693/Ka
What is a mathematical check to verify the method of residuals?
Ka/Kel = 5+ (needs to be greater than 5)
How do we calculate the volume of distribution using the method of residuals if we do not know the bioavailability of the drug?
Rearrange the bateman function for (V/F)
How do we calculate the clearance using the method of residuals if we do not know the bioavailability of an orally administered drug?
Use CL/F = Kel/(V/F)
How can we approximate AUC?
Bioavailability * Dose
Remember: AUC is the cumulative systemic exposure of a drug.
How do you determine the absolute Bioavailability of a drug?
By comparing the AUC (oral) to the AUC (IV).
See page 8 of study guide for formula.
What is relative bioavailability and how do we calculate it?
Relative bioavailability is used to compare two oral formulations, particularly when there is not an IV formulation available for use.
See page 8 of study guide for formula.
What are the determinants of Tmax
Ka, Kel (CL, V)
See page 9 of study guide for equation.
What are the determinants of Cmax
D,F,Tmax (ka, CL, V)
See page 9 of study guide for equation.
How do you calculate AUC?
(Bioavailability * Dose) / Clearance
What formula do we use to calculate the plasma concentration of a drug following multiple dose administration?
See page 10 of study guide.
How do we calculate the minimum concentration at steady state of a drug following multiple dose administration?
See page 10 of study guide.