L1 - Fundamental Concepts in PK Flashcards
Name the different sites of measurement , and whether they are invasive (I), or non-invasive (NI).
Plasma, serum, blood - invasive
breath, milk, saliva, urine, faeces - non-invasive
What are the differences between plasma, serum and whole blood?
Plasma - whole blood is centrifuged after adding an anticoagulant, cells are precipitated. Plasma contains proteins that often bind drugs, as well as bound and unbound drugs in circulation.
Serum - whole blood is centrifuged after blood has been clotted. Cells and material forming the clot, including fibrinogen and its clotted form, fibrin, are removed.
Whole Blood - contains red blood cells, white blood cells, platelets and various plasma proteins. Anticoagulant is added, drug is commonly extracted into an organic phase after denaturing the plasma proteins.
How to calculate plasma-to-blood concentration ratio at equilibrium?
1 / 1+ H[fu x Kprbc -1]
(T/F): Fraction unbound, fu of drug always remains constant.
False. Fu usually remains constant, but there are cases when protein binding is altered.
These cases include:
- renal disease, hepatic disease, surgery, severe burns and pregnancy.
The higher the AUC of a given oral dosage regimen, the greater is its absolute oral bioavailability. Is this statement true, false or partially true?
Absolute oral bioavailability, F = AUC(PO)/AUC(IV)
Assuming we are comparing against a constant AUCiv, an increase in AUC(PO) –> increase in F.
This statement is true.
That being said however, one must be clear that AUC(PO) is not the same as F.
ADME represents absorption, distribution, metabolism and elimination of drug in pharmacokinetics. Is this statement true or false?
False. E stands for excretion and not elimination.
Elimination = metabolism + excretion
Drug administered orally is systemically absorbed while drug administered intramuscularly is not systemically absorbed.
False. Drugs administered through IM can still end up in the blood circulation after the leave the site of absorption and enter the blood.
A drug that is absorbed from the intestinal lumen into the intestinal enterocytes is considered to be systemically absorbed. Is this statement true or false?
False. A drug that is administered orally can be systemically absorbed after it enters the hepatic vein (note that this is not the hepatic portal vein).
A drug that is biliary excreted is completely eliminated from the systemic circulation. Is this statement true, false or impossible to establish without further information?
Impossible to establish without further information. Drug could have been reabsorbed via enterohepatic recycling or recirculation.
Describe the different pathways of elimination that transpire from the gut lumen to the site of measurement.
Gut lumen: metabolism and to faeces
Gut wall: metabolism
Portal vein and liver: metabolism and biliary excretion
Site of measurement: systemic absorption
What phases does disposition cover?
distribution + elimination
Define the enterohepatic cycle.
Process where drug is secreted into bile, stored in and released from the gallbladder, before transiting into the small intestine and being reabsorbed there back into circulation.
Considered a component of distribution.
Define elimination.
Elimination is the irreversible loss of drug from the site of measurement.
What are the principal organs of elimination and the processes that occur there?
Liver (metabolism: conversion of one chemical species to another)
Kidney (excretion: irreversible loss of chemically unchanged drug)
Define metabolism, the different phases in metabolism and the major sites of metabolism?
Metabolism is the conversion of the parent drug to another chemical species (metabolite).
Different phases of metabolism that render a drug inactive and ready for excretion:
- Phase I reactions: oxidation, reduction, hydrolysis
- Phase II reactions: conjugation with polar endogeneous compounds to render substance more water-soluble
Major sites of metabolism include: intestinal mucosa and liver
