RxPrep Pharmacokinetics

pharmacokinetics

what the human body does to a drug during the processes of drug absorption, distribution, metabolism, and excretion

pharmacodynamics

what the drug does to the human body; refers to relationship between the drug concentration at the site of action and both therapeutic and adverse effects

intravascularly

When a drug is given (extravascularly/intravascularly), absorption is not required.

extravascularly

If a drug is given (extravascularly/intravascularly), drug absorption occurs.

small intestine

Most oral drug absorption occurs in the ________ because of the large surface area and permeable membrane.

portal vein; liver

After gut absorption, a drug enters the ________ and travels to the ________.

first-pass metabolism

extensive metabolism of a drug by the liver

enterohepatic recycling

drug transported through the bile back to the gut where they can be reabsorbed

passive diffusion

movement of drugs from an area of high concentration to an area of lower concentration

active transport

drugs are moved across the gut wall via transporter proteins that are normally used to absorb nutrients from food

disintegration

process of a solid oral dosage form breaking into smaller pieces in the GI tract

dissolution

process of the smaller pieces of a solid oral dosage form dissolving and releasing the active ingredient from the dosage form

Noyes-Whitney

The rate of dissolution is described by the ________ equation.

ODT, SL tablet

What 2 solid dosage forms generally have fast absorption?

c; e; d; b; a

Put the following dosage forms in order of the fastest to slowest rate of absorption.

a) extended-release tablet

b) immediate-release tablet

c) IV

d) ODT

e) SL

sublingual

What does SL stand for?

orally-disintegrating tablet

What does ODT stand for?

hydrolysis

Most immediate-release formulations dissolve and get absorbed rapidly, but some can be destroyed in the gut, primarily by ________.

enteric-coated

drug formulation developed with protective coating to limit drug degradation in the stomach (acidic) and permit dissolution in the intestine (basic)

particle diameter; surface area

If a drug has poor absorption, one of the methods used to increase the dissolution rate is to reduce ________, which increases ________.

micronized

Drugs with very small particle diameters are referred to as ________.

solubility

The rate and extent to which a drug dissolves in GI fluids depends on the drug's ________.

dissolved

As a drug moves through the GI tract, only ________ drug is absorbed into the bloodstream.

bioavailability

extent of drug absorption into the systemic circulation; reflects the percentage of drug absorbed from extravascular compared to intravascular administration

high; >70

A drug with good absorption has (high/low) bioavailability (________%).

low; <10

A drug with poor absorption has (high/low) bioavailability (________%).

levofloxacin, linezolid

________ and ________ have high bioavailability; nearly 100% of the oral dose is absorbed, and the oral and IV doses are the same.

area under the plasma concentration time curve

What does AUC stand for?

absolute bioavailability

What does "F" stand for?

100 x (AUC extravascular / AUC intravenous) x (DOSEintravenous / DOSEextravascular)

What is the equation for F?

57%

100 x (8 / 4.2) x (15 / 50) = 57

A pharmacokinetic study of an investigational drug was conducted in healthy volunteers. Following an IV bolus dose of 15 mg, the AUC was determined to be 4.2 mg x hr/L. Subjects were later given an oral dose of 50 mg and the AUC was determined to be 8 mg x hr/L. Calculate the absolute bioavailability of the investigational drug. (round to nearest whole number)

amount absorbed from current dosage form / F of new dosage form

What equation is used to calculate an equivalent dose of a drug when the dosage form is changed?

distribution

the process by which drug molecules move from the systemic circulation to various tissues and organs

high lipophilicity, low molecular weight, low protein binding, unionized

What are 4 factors that favor passage across membranes and greater drug distribution to the tissues?

albumin

What is the primary plasma protein responsible for drug binding?

unbound

The (bound/unbound) form of the drug is the "free" form.

unbound

Only (bound/unbound) forms of a drug can interact with receptors, exert therapeutic or toxic effects, and be cleared from the body.

unbound

If a drug is highly protein-bound and serum albumin is low, then a higher percentage of the drug will be in the (bound/unbound) form.

calcium, phenytoin

What are 2 examples of highly protein bound compounds that require an adjustment of the total level?

correction

________ formulas allow us to determine what the concentration would be if albumin was normal for a high protein bound drug.

higher

With hypoalbuminemia, the corrected level of a highly protein bound drug will be (higher/lower) than the total level reported by the lab.

free phenytoin, ionized calcium

What 2 lab levels only measure the unbound portion of highly protein bound drugs, meaning no adjustment calculations will be required for hypoalbuminemia?

0.8(4 - albumin) + Ca

What is the equation for corrected calcium?

phenytoin / [(0.2 x albumin) + 0.1]

What is the equation for corrected phenytoin?

c, e

A pharmacist receives a call from a provider asking for assistance with 2 patients in the clinic. Both patients have a seizure disorder and are taking phenytoin. Patient A is seizure free, but is experiencing symptoms of toxicity. Patient B has a higher phenytoin level and is doing fine. Both patients have normal renal function. Which of the following statements is/are true of this scenario? (select all that apply)

Patient A

phenytoin (10-20 mcg/mL): 14.3

albumin (3.5-5 g/dL): 2.1

Patient B

phenytoin (10-20 mcg/mL): 17.8

albumin (3.5-5 g/dL): 4.2

a) Patient B's corrected phenytoin level will be lower than the total level reported.

b) Patient A's corrected phenytoin level will be lower than the total level reported.

c) Patient A's corrected phenytoin level will be higher than the total level reported.

d) Patient A has a greater percentage of bound phenytoin.

e) Patient A has a greater percentage of unbound phenytoin.

volume of distribution

What does "V" or "Vd" stand for?

Vd

reflects how large of an area in the patient's body the drug has distributed into and is based on the properties of the drug; relates amount of drug in the body to the concentration of the drug measured in plasma

amount of drug in body / drug plasma concentration

What is the equation for Vd?

20 L

500 / 25 = 20

A 500 mg dose of gentamicin is administered to a patient, and a blood sample is drawn. The concentration of gentamicin is measured as 25 mcg/mL (which is the same as 25 mg/L). What's the Vd of gentamicin in this patient?

metabolism

process by which a drug is converted from its original chemical structure into other forms to facilitate elimination from the body

gut, liver

What are 2 primary sites for drug metabolism?

decrease

First-pass metabolism can dramatically (decrease/increase) the bioavailability of an oral formulation.

lidocaine

First-pass metabolism of ________ is so extensive that the drug cannot be given orally, it must be given IV.

I; II

Drug metabolism involves Phase (I/II) reactions followed by Phase (I/II) reactions.

I

Oxidation, reduction, and hydrolysis are examples of Phase (I/II) reactions.

II

Conjugation and glucuronidation are examples of Phase (I/II) reaction.

hydrophilic

Breaking carbon bonds or adding a hydroxyl group to a drug makes the drug more (hydrophilic/lipophilic), meaning more of the drug stays in the blood.

excretion

process of irreversible removal of drugs from the body

acidifying

For a drug that's a weak base, excretion can be increased by (acidifying/alkalinizing) the urine.

alkalinizing

For a drug that's a weak acid, excretion can be increased by (acidifying/alkalinizing) the urine.

clearance

What does "Cl" stand for?

Cl

the rate of drug removal in a certain volume of plasma over a certain amount of time; efficiency of drug removal from the body

steady

Most drug elimination occurs at a (changing/steady) rate.

rate of elimination

rate at which drug is being removed from the body at any time

rate of elimination / drug concentration

What is the equation for Cl?

6 L/hr

(300 / 4) / 12.5 = 6

A dose of gentamicin is given to a patient, and urine is collected from the patient for 4 hours after drug administration. It's determined that 300 mg of gentamicin was eliminated during that time period, and the measured plasma concentration at the midpoint of the collection was 12.5 mg/L. Calculate the patient's gentamicin clearance.

AUC

What is the most reliable measurement of a drug's bioavailability?

(F x dose) / AUC

What is the equation used for Cl for extravascular administration when using AUC?

dose / AUC

What is the equation used for Cl for intravenous administration when using AUC?

5 L/hr

400 / 80 = 5

A patient is currently receiving 400 mg of gentamicin IV once daily, and, based on measured serum concentrations, the AUC is determined to be 80 mg x hr/L. Calculate the patient's gentamicin clearance.

first

Most drugs follow (first/zero)-order elimination.

first-order elimination

a constant percentage of drug is removed per unit of time

zero-order elimination

a constant amount of drug (mg) is removed per unit of time

phenytoin, theophylline, voriconazole

What are 3 examples of drugs that exhibit Michaelis-Menten kinetics?

non-linear, saturable

What are 2 other terms for Michaelis-Menten kinetics?

maximum rate of metabolism

What does Vmax stand for?

Michaelis-Menten constant

What does Km stand for?

Km

concentration at which the rate of metabolism is half maximal

first

At very low concentrations relative to the Km, the rate of metabolism of Michaelis-Menten drugs mimics (first/zero)-order processes.

zero

At very high concentrations relative to the Km, the rate of metabolism of Michaelis-Menten drugs mimics (first/zero)-order processes.

b

With Michaelis-Menten kinetics, an increase in dose leads to a ________ in drug concentration at steady state.

a) disproportionate decrease

b) disproportionate increase

c) proportionate decrease

d) proportionate increase

small

Because the rate of phenytoin metabolism approaches the maximum at accepted therapeutic concentrations, phenytoin dose adjustments should be made in (large/small) increments when the serum concentration is >7 mcg/mL.

linear

What's another term for first-order kinetics?

first

With (first/zero)-order kinetics, doubling the dose at steady state approximately doubles the serum concentration.

e

A patient has been using phenytoin 100 mg TID. A phenytoin level was drawn and found to be 8.8 mcg/mL (reference range 10-20 mcg/mL). The dose was doubled to 200 mg TID. The patient started to slur her words, felt fatigued, and returned to the clinic. The level was repeated and found to be 23.7 mcg/mL. Which of the following statements is accurate regarding the most likely reason for the change in phenytoin level?

a) Phenytoin half-life is reduced at higher doses.

b) Phenytoin volume of distribution increases at higher doses.

c) The patient's serum albumin level likely increased.

d) Phenytoin bioavailability can decrease at higher doses.

e) Phenytoin metabolism can become saturated at higher doses.

elimination rate constant

What does ke stand for?

ke

fraction of drug that's eliminated (cleared) per unit of time

Cl / Vd

or [ln (C1 / C2)] / t

What are 2 equations for ke?

0.1 hr^-1

5000 mL / 1000 mL = 5 L

5 / 50 = 0.1

A drug has the following pharmacokinetic parameters: Vd = 50 L and Cl = 5,000 mL/hr. Calculate the elimination rate constant of the drug.

10

If ke is 0.1 hr^-1, then ________% of the drug remaining is cleared per hour.

C1 x e^(-kt)

What is the equation for C2?

1.72 mg/L

10 x e^(-0.22 x 8) = 1.72

A patient received a dose of gentamicin. A short time after the end of the infusion, it's known that the drug level was 10 mg/L, and the patient's ke = 0.22 hr^-1. Calculate the predicted concentration after 8 hours. (round to nearest hundredth)

4 hrs

15 = 28 x e^(-0.15 x t)

(15 / 28) = e^(-0.15 x t)

ln(15 / 28) = -0.15t

t = 4

A patient being treated with vancomycin had a supratherapeutic trough level of 28 mcg/mL. If ke = 0.15 hr^-1, predict how long it will take for the trough to decrease to the goal therapeutic trough (15 mcg/mL). (round to nearest hour)

half-life

time required for a drug concentration (and drug amount) to decrease by 50%

0.693 / ke

What is the equation for t1/2?

half-life

What does t1/2 stand for?

steady-state

point at which the rate of drug intake equals the rate of drug elimination

5

It takes ~________ half-lives to reach steady state, assuming the drug follows first-order kinetics in a one-compartment distribution model and no loading dose has been given.

95

5 half-lives are required to eliminate more than ________% of the drug if no additional doses are given.

steady-state

The most clinically useful information is obtained from drug levels collected at ________.