extravscular concepts

what governs drug absorptiion?

1. physicochemical and biochemical properties of the drug molecule (drug factor)

2. API

3. dose form (drug factor)

4. drug delivery

5. anatomy and physiology of ABSORPTION site

6. characteristics of body (patient factor)

drug absorption is characterized as ___ ____ or ____ _____ process

first order or zero order

Drurg absorption into systemic cireculation after oral dosing of solid dosage form encounters MULTIPLE rate proccesses:

• _______ of solid dosage form in the GU tract

• GI ________ (helps movement of drug from stomach to small intestine)

• drug ____________

• permeability across the ____________

• transverse across the intestinal capillaries INTO ______ blood

• first pass removal (metabolism) by ______ or _______

• reach SYSTEMIC circulation

• disentegration

• motility

• dissolution

• enterocytes

• portal

• liver small intestine

______ membrane of the enterocyte faces the blood

basal

___________ membrane of the enterocyte faces the inside of the lumen

apical

_____________ is a pre requisite to move across the gut wall

dissolution

fraction of extravascular dose that reaches the systemic circulation

bioavailability

how is the rate of change of the drug in the blood different for intravenous vs extravascular administration?

IV = -Kel * A

oral = Ra - Kel (A)

in oral the drug first accumulates in the blood through absorption (Ra) THEN it begins to be eliminated based on its remaining concentration

rate of absorption is proportional to the amount AVAILABLE to be absorbed

first order

rate = -ka x Agut

amount of drug left in gut to be absorbed

what is different between first order and zero order drug absoption?

first order: rate of absorption depends on how much has yet to be absorbed

zero order: the rate of absorption is constant disregarding how much drug is left in the gut to be absorbed

what is lag time

the time it takes for an oral drug to finally absorb and make its way into the systemic circulation (NOT right away)

bioavailability is the fraction of _________ drug that reaches systemic circulation

unchanged

in flip flop kinetics which is kel or kab greater?

elimination is ________-rate limited

Kel greater in flip flop usually absorption is greater

absorption

in normal kinetics which is kel or kab greater?

elimination is ________-rate limited

ka usually greater than Kel

disposition

as the dose decreases what happens to the

• peak concentration

• AUC

• peak time

• peak concentration decrease (less drug to come in blood)

• AUC decreases (less drug spending time in body)

• peak time REMAINS SAME (the time to reach even lower concentrations is the same as higher concentration reaching peak in blood)

If you increase dose what happens to

• AUC

• Cl

• Vd

• Cmax

AUC and Cmax ALSO increase

Vd and Cl are INDEPENDENT OF DOSE