Volume of Distribution
This pharmacokinetic parameter describes the apparent volume needed to contain the drug at the same concentration as plasma.
What is volume of distribution (Vd)?
Greater blood flow to tissues produces this effect on drug distribution.
What is increased/faster distribution?
This form of a drug is pharmacologically active and able to cross membranes.
What is the free (unbound) drug?
First-pass metabolism primarily occurs in this organ.
What is the liver?
A hydrophilic antibiotic remains mostly in the bloodstream and has a Vd of 4 L. The drug is primarily located in this body compartment.
What is plasma (intravascular space)?
This is the equation used to calculate Vd.
What is Vd = Amount of drug in body ÷ Plasma concentration (Cp)?
These openings between endothelial cells increase permeability in organs such as the liver and spleen.
What are fenestrae?
Warfarin is approximately this percent protein bound.
What is 99%?
A drug with F = 0.25 requires a 100 mg IV loading dose. What oral dose would achieve the same exposure?
What is 400 mg?
A drug is 99% protein bound. Only this fraction is able to cross membranes and produce pharmacologic effects.
What is 1% the free (unbound) fraction?
A drug confined mainly to plasma will have this type of Vd: small or large?
What is a small Vd?
This specialized barrier limits the entry of many drugs into the brain.
What is the blood–brain barrier?
Protein-bound drugs can or cannot easily diffuse across membranes?
What is cannot?
A drug has excellent intestinal absorption but low oral bioavailability of 20%. This pharmacokinetic process most likely explains the discrepancy.
What is first-pass metabolism?
A patient stabilized on warfarin begins aspirin therapy. Two days later, the INR rises and bleeding occurs. This pharmacokinetic mechanism explains the interaction.
What is displacement from plasma protein binding increasing the free fraction of warfarin?
High lipid solubility and extensive tissue binding generally produce this type of Vd.
What is a large Vd?
Drugs distribute first to highly perfused organs such as these four.
What are heart, liver, kidney, and brain?
Drug + protein forms this reversible structure in plasma.
What is the drug–protein complex?
A drug has an oral bioavailability of 10% due to extensive first-pass metabolism, but rapid systemic action is required. Name TWO alternative routes that would most improve systemic availability.
What are intravenous and sublingual (or inhalation/buccal/transdermal acceptable with justification)?
A patient overdoses on a highly lipid-soluble drug with a Vd of 400 L. Hemodialysis is attempted but ineffective. This pharmacokinetic property explains why dialysis fails.
What is a very large volume of distribution with extensive tissue binding?
A 500 mg dose produces a plasma concentration of 10 mg/L. Calculate Vd
What is 50 L?
Obese patients often show larger Vd for these types of drugs.
What are lipid-soluble (fat-soluble) drugs?
Competition for binding sites may increase this fraction of a displaced drug.
What is the free fraction?
Food delays gastric emptying and decreases rate but not extent of absorption. Which PK parameter changes: Cmax, Tmax, or AUC?
What is Tmax (and possibly Cmax), but not AUC?
A 70-kg patient requires a target plasma concentration of 10 mg/L. The drug’s Vd is 0.7 L/kg. Calculate the loading dose required.
What is 490 mg?
Working:
Vd = 0.7 × 70 = 49 L
LD = Cp × Vd = 10 × 49 = 490 mg