Pharmacokinetics II Flashcards
What is bioavailability?
Amount of free and active unchanged drug that reaches systemic circulation
What mechanism of drug administration typically has 100% absorption?
IV
What mechanism of drug administration rarely has 100% absorption?
any non-IV route
What can the bioavailability be used to calculate clinically?
The equally effective dose between two different routes of administration
How do you calculate effective IV dose?
D(iv) = D(oral) x [bioavailability/100]
How do you calculate effective oral dose?
D(oral) = D(iv) / [bioavailability/100]
A drug has an oral bioavailability of 40%. An effective oral dose is 100mg. What is the equivalent IV dose?
40mg
An effective IV dose is 100mg
and has a bioavailability of 40%. What is the equivalent oral dose?
250mg`
What is the first-pass effect?
Following oral administration, a significant amount of drug enters the portal blood and may be metabolized in the liver before it reaches the systemic circulation.
Inter-patient variation in ____ can affect plasma drug levels after administration of drugs that have a high first-pass effect.
Hepatic function
What is the volume of distribution (Vd)?
Relates the amount of drug in the body to the amount of drug in the blood
What is the single compartment model?
Apparent volume
that a drug would need to be dissolved in to maintain a homogeneous concentration throughout the body
If a drug is distributed extensively and bound to peripheral tissues, does that indicate a large or small Vd?
Large Vd
If a drug is highly concentrated in the plasma, does that indicate a large or small Vd?
Small Vd
What compartment of the body does a Vd of 3-5L correlate to?
Plasma water (warfarin)
What compartment of the body does a Vd of 10-20L correlate to?
Extracellular space (aspirin)
What compartment of the body does a Vd of 22-40L correlate to?
Whole body water
What compartment of the body does a Vd of >70L correlate to?
Tissue
What are biological storage depots?
Sites in the body can accumulate drugs and act as reservoirs; affecting distribution by decreasing plasma levels and prolonging half-lives.
What type of drugs accumulate in adipose tissue?
Highly lipid soluble drugs
What kind of drugs accumulate in tissues?
Drugs that bind reversibly to cellular components
What kind of drugs accumulate in bone?
Drugs with chelating properties
What kinds of drugs accumulate in transcellular reservoirs?
Drugs that are slowly absorbed or undergo enterohepatic circulation
What kind of drugs accumulate in the plasma and have prolonged half-lives?
Drugs that have high plasma protein
(albumin) binding
If a drug is available but not active does that indicate a low or high Vd?
Low Vd (warfarin)
What kind of drugs commonly use redistribution?
Lipid soluble drugs are distributed between compartments
What type of drugs accumulate in breast milk?
Breaks milk is more acidic than plasma, so basic and lipid soluble drugs get trapped
What are common sites of drug exclusion in the body?
Fluids!
Cerebrospinal fluid; ocular fluid; fetal fluid; pleural fluid
What type of drugs are teratogenic?
Fetus is acidic, so basic drugs get trapped
What occurs by first or zero order kinetics?
Elimination
First order elimination compares what?
Percentage of the drug eliminated/time
What is the rate limiting factor of first order elimination?
Plasma concentration
What is half-life?
Time required to decrease the plasma concentration by 50%
How do you calculate half -life?
t1/2 =(0.7xVd)÷CL
What is the t1/2 of a drug with Vd = 40 L and CL of 5 L/hr?
*if given in L assume the patient is 70kg
t = (0.7 x 40 L) ÷ 5 L/hr = 5.6 hr
What is the t1/2 if Vd = 0.57 L/Kg and CL of 5 L/hr in a 80 Kg man?
t1/2 = (0.7 x 0.57 L/Kg x 80 Kg) ÷ 5 L/hr = 6.4 hr
How long does it take to eliminate most of a drug?
5 half-lives
How long does it take to obtain Css (concentration steady-state) plasma levels?
5 half-lives
Is the time to reach Css related to size of dose?
NO DUMB BITCH
Is the time to reach Css related to half-live?
YASSS QUEEN
What will result in increased Css?
Shortening the dosing interval (τ) or increasing the dose (D)
What will result in decreased Css?
Lengthening the dosing interval (τ) or decreasing the dose (D)
What is zero order elimination?
Constant amount eliminated over unit time
What type of elimination has the biological system as the rate limiting factor and is not dependent upon plasma levels or dose?
Zero order elimination
For a drug with zero order kinetics, if given repeatedly in high doses, will it develop steady state levels?
No, because it is not dependent on plasma levels
For a drug with zero order kinetics, if given at higher doses than its elimination rate, will it accumulate in the body?
Yes, it will accumulate and produce excessive plasma levels and toxicity
What is clearance?
Measure of body’s capacity to eliminate a drug
How do you calculate clearance (CL)?
CL=Vd x (0.7÷t1/2)
What is the CL of a drug with a Vd = 100 L and t1/2 = 2 hr?
*if given in L assume the patient is 70kg
35 L/hr
What is the CL if Vd = 100 L and t1/2 = 2 hr in a 80 Kg patient?
40 L/hr
What is directly proportional to Css?
Dose (D), bioavailability(F), and half-life (τ)
What is inversely proportional to Css?
Clearance (CL), and volume distribution (Vd)
What is the goal of a maintenance dose?
Drugs are administered in a way so we maintain a steady state concentration (Target Concentration) in the body
Maintenance dose = elimination rate
How do you calculate maintenance dose?
Maintenance dose = (CL x TC ÷ F) x dosing interval (τ)
What is used to achieve immediate therapeutic plasma concentrations (Css)?
Loading dose (LD)
How do you calculate loading dose?
LD = Vd x TC
What is the LD if Vd = 100 L and TC = 5 mg/L?
*if given in L assume the patient is 70kg
LD = 100 L x 5 mg/L = 500 mg
What is the LD if Vd = 100 L and TC = 5 mg/L in a 60 Kg patient?
Vd = 100 L ÷ 70 Kg = 1.42 L/Kg
LD = 1.42 L/Kg x 5 mg/L x 60 Kg = 426 mg
What are some differences between brand name and generic drugs?
Brand name drugs
• Name is protected forever (Tylenol)
• Compound is protected for 20 years (acetaminophen)
• Few exceptions orphan drugs
Generic drugs
• Contain the same active ingredient(s)
• Less expensive
`A 23 year old man goes to a party and consumes 5 vodka tonics in the first 10 min he is there. If each drink contains ~10g of ethanol, approximately how long does he have to wait to ensure that his blood alcohol content level is 0.0?
5 hours
A drug a has an oral bioavailability of 70%. You want to switch the patient from the effective 350 mg IV dose to oral dosing. The equally effective oral dose is:
D(oral) = 350 ÷ 0.7 = 500mg
Whats an example of a drug with a high first pass?
Isoniazid
Whats an example of a drug with a low first pass?
Diazepam
At what rate is ethanol eliminated?
10g/hr
