pharmacokinetics II, lecture 6 Flashcards
bioavailability
amount of free and active unchanged drug that reaches systemic circulation
what is the absorption after IV administration?
100%
How do you calculate the Dose (IV) if you are given Dose (oral) and % bioavailability
DIV = Doral x [Bioabailability (%) / 100]
How do you calculate bioavailability (F) if you are given AUCoral and AUCIV
Bioavailability (F) = [AUCOral / AUCIV] x 100
this constant relates the amount of drug in the body to the amount of drug in the blood
volume of distribution (Vd)
There are two ways to calculate Vd (volume of distribution). Give both
- Vd = [total amount of drug in the body]/[concentration in plasma]
- Vd= intravenous dose / plasma concentration of drug at time zeo (C0)
drugs that distribute extensively and bind to peripheral tissues have a large or small Vd
large Vd
Drugs that are highly concentrated in the plasma have a large or small Vd
small Vd
Vd is affected by several factors. Name them
- age
- body weight
- organ pathology
if a drug’s Vd lies in the 3-5 L range, where is it found in the body
plasma water
Warfarin has what Vd concentration
Vd = 3-5 L which means it is highly concentrated in the plasma water
If a drug has a Vd that lies in 10-20 L range, where is it highly concentrated?
extracellular space
If a drug has a Vd that lies in 22-40 L range, where is it highly concentrated
whole body water
If a drug has a Vd that lies in >70 L range, where is it highly concentrated
Tissue
When you make Vd calculations, what weight for the patient is assumed?
70 Kg
Ex: 200 mg of Drug A is administered IV. Plasma concentration was 5 mg/L at time zero. Calculate the Vd in an 80 Kg patient
- Vd = DIV / C0
- Vd= 200 mg / 5 mg/L = 40L
- Determine Vd in a single Kg: 40L / 70 kg = 0.57 L/kg
- multiply by weight of patient: 0.57 L/kg x 80 kg = 45 L
what are biological storage depots
sites in the body that can accumulate drugs and acts as reservoirs; affecting distribution by decreasing plasma levels and prolonging half-lives
What type of drugs accumulate in fat
highly lipid soluble drugs
What type of drugs accumulate in tissues
drugs that bind reversibly to cellular components
What type of drugs accumulate in bone
drugs with chelating properties
what type of drugs accumulate in transcellular reservoirs such as GI tract
drugs that are slowly absorbed or undergo enterohepatic circulation
drugs that have high plasma protein (albumin) binding have a high or low Vd
- low Vd
- these drugs accumulate in plasma and have prolonged half-lives
- they are available but not active
what type of drugs can be distributed between compartments (e.g. from plasma to muscle and adipose tissue).
lipid soluble drugs
what type of drugs will accumulate in breast milk? Why?
- breast milk is more acidic than plasma
- basic and lipid soluble drugs will accumulate
what are the sites that drugs are often unable to penetrate
- cerebrospinal fluid
- ocular fluid
- fetal fluid
- pleural fluid
what type of drugs can be transfered from pregnant mother to fetus. why?
- fetus is acidic
- basic drugs will get trapped (can be teratogenic)
what is first order elimination
a certain percentage of the drug is eliminated per amount of time
what is the rate limiting factor in first order elimination
plasma concentration
what is the relationship between half life (t1/2) and Vd and CL (clearence)
t1/2 = (0.7 x Vd) / CL
What is the relationship between t1/2 and Kel (elimination constant)
t1/2 = 0.7 / Kel
What is the t1/2 of a drug with Vd = 40L and CL 5L/hr?
- t1/2 = (0.7 x 40L) / 5L/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) / 5L/hr = 6.4 hr
if first order elimination, how long does it take (in t1/2) to eliminate most of a drug? How long does it take to obtain Css plasma levels?
- 5 t1/2
- 5 t1/2
in first order elimination, the time to reach Css is related to dose and/or t1/2?
- only to t1/2, NOT dose
if you are working with a first order kinetics drug, what changes to the dosing interval and the dose concentration will result in an increased steady state
- shorten the dosing interval
- increasing the dose
How can you differentiate between a first order and zero order kinetics plot in a logarithmic form?
- zero order: curved line
- first order: straight line
what is zero order elimination
constant amount eliminated over unit time
what is the rate limiting factor in a zero-order reaction
- biological system is the rate limiting factor
- it is not dependent on plasma levels or dose
in a zero order elimination, if you repeatedly give a high dose, will steady state levels develop? why or why not?
- will NOT develop steady state levels
- zero order kinetics is not dependent on plasma levels
what happens if a first order elimination drug is given at higher doses then its elimination rate?
will accumulate in the body and produce excessive plasma levels and toxicity
what is clearance (CL)
measure of body’s capacity to eliminate a drug
What is the relationship between Vd and CL and Kel (elimination constant)
CL = Vd x Kel
What is the equation between total systemic clearance
CL = CL renal + CL hepatic + CL lung + CL others
what is the CL of a drug with Vd = 100 and t1/2 = 2 hr
- T1/2 = (0.7 x Vd) / CL therefore CL = Vd x (0.7 / t1/2)
- CL = 100L (0.7 / 2 hr) = 35 L/hr
What is the CL if Vd=100L and t1/2= 2 hr in a 80 kg patient
- Vd = 100L / 70 kg = 1.43 L/kg
- CL = 1.43 L/kg x (0.7 / 2 hr) = 0.44 L/hr/Kg
- CL = 0.5 L/hr/Kg x 80 Kg = 40 L/hr
Css has what relationship to dose, bioavailability, t1/2, CL and Vd?
- Css is directly proportional to dose, bioavailability, and t1/2
- Css is inversely proportional to CL and Vd
if drug infusion is stopped, how long does it take for your body to eliminate a drug
5 and 1/2 t1/2 to eliminate drug
when drug infusion is started, how long does it take to reach concentration steady state
5 and 1/2 half lives
what can be administered to achieve an immediate therapeutic plasma concentration
a loading dose
what equation will allow you to determine LD (loading dose)
LD = Vd x TC (Css)
once the loading dose is administered, what dose can be given to maintain steady state concentration
proper maintenance dose
What is the loading dose if Vd = 100 L and TC = 5 mg/L
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 = 100L / 70 kg = 1.42 L/kg
- LD = 1.42 L/kg x 5 mg/L x 60 kg = 426 mg
how can you determine the maintenance dose?
- maintenance dose = dosing rate x dosing interval
- maintenance dose = (CL x TC / F) x dosing interval
If you increase the dose and dosing interval by the same ratio, what happens to the Css
no change
at concentration steady state, how can you determine the dosing rate using clearance, theraputic concentration and bioavailability of a drug
- dosing rate = elimination rate = CL x TC / F
- ** F = 1.0 if administration is IV
determine the dosing rate for a drug that is infused and the desired TC is 100 mg/L. the CL is 2.0 L/hr
DR = (2.0 L/hr x 100 mg/L) / 1 = 200 mg/hr
how long is a compound protected when it is first made
20 years, then companies can make generic form
