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

D_{IV} = D_{oral} x [Bioabailability (%) / 100]

How do you calculate bioavailability (F) if you are given AUC_{oral} and AUCIV

Bioavailability (F) = [AUC_{Oral} / AUC_{IV}] x 100

this constant relates the amount of drug in the body to the amount of drug in the blood

volume of distribution (V_{d})

There are two ways to calculate Vd (volume of distribution). Give both

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- 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

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- 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

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- Vd = D
_{IV} / 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

_{IV}/ C0what 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

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- 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?

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- 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

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- cerebrospinal fluid
- ocular fluid
- fetal fluid
- pleural fluid

what type of drugs can be transfered from pregnant mother to fetus. why?

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- 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)

t_{1/2} = (0.7 x Vd) / CL

What is the relationship between t_{1/2} and K_{el} (elimination constant)

t_{1/2} = 0.7 / K_{el}

What is the t_{1/2 }of a drug with Vd = 40L and CL 5L/hr?

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- t
_{1/2} = (0.7 x 40L) / 5L/hr = 5.6 hr

_{1/2}= (0.7 x 40L) / 5L/hr = 5.6 hrwhat is the t_{1/2} if Vd= 0.57 L/Kg and CL of 5 L/hr in a 80 Kg man

t_{1/2} = (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 t_{1/2}) to eliminate most of a drug? How long does it take to obtain Css plasma levels?

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- 5 t
_{1/2}
- 5 t
_{1/2}

_{1/2}_{1/2}in first order elimination, the time to reach Css is related to dose and/or t_{1/2}?

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- only to t
_{1/2}, NOT dose

_{1/2}, NOT doseif 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

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- shorten the dosing interval
- increasing the dose

How can you differentiate between a first order and zero order kinetics plot in a logarithmic form?

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- 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

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- 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?

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- 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 t_{1/2} = 2 hr

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- T1/2 = (0.7 x Vd) / CL therefore CL = Vd x (0.7 / t
_{1/2})
- CL = 100L (0.7 / 2 hr) = 35 L/hr

_{1/2})What is the CL if Vd=100L and t_{1/2}= 2 hr in a 80 kg patient

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- 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, t_{1/2}, CL and Vd?

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- Css is directly proportional to dose, bioavailability, and t
_{1/2}
- Css is inversely proportional to CL and Vd

_{1/2}if drug infusion is stopped, how long does it take for your body to eliminate a drug

5 and 1/2 t_{1/2} 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

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- 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?

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- 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

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- 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