PK Exam 1

PK

how the body handles the drug

PD

how the drug affects the body

systemic absorption

medication moves from administration site into systemic circulation, travels through entire body to reach target site

distribution

drug getting spread throughout the body (reversible)

disposition

what happens to drug after it’s in the body (how body treats drug)

Absorption

how drug enters body

Distribution

drug traveling from blood to target site

metabolism

process of changing the drug through chemical processes

excretion

how the body removes the drug

clearance (CL)

theoretical volume of blood completely cleared of drug per unit time

clearance units

L/min

clearance = ?

blood flow to organ x extraction ratio

extraction ratio

the fraction of drug removed from blood by an organ in one pass

• higher means more drug removed

volume of distribution

hypothetical volume to represent the volume the drug takes up in the body

What does a small volume of distribution mean?

drug stays in bloodstream

Vd (L) = ?

dose (mg) / concentration (mg/L)

elimination rate constant (Kel)

estimation of the fraction of total drug removed per unit time

• how fast drug leaves body

Kel units

time^-1

half-life

always a constant

used to estimate time to reach steady-state (infusion) or time to be eliminated (bolus)

primary parameters

clearance and volume of distribution

secondary parameters

Kel and T ½

derived from CL and Vd

Kel = ?

CL/V

T ½ = ?

0.693 / Kel

compartmental analysis

body parts lumped into 1 or more homogenous compartments that are kinetically connected

nonlinear regression analysis

non-compartmental analysis

estimates drug exposure and elimination directly from observed concentration–time data, without assuming compartments

SHAM

slope, height, area, moment

slope

represented by k

inverse of Kel

height

determines max concentration after administration and absorption

AUC

shows full drug exposure after each dose

moment

any given time on the graph

transcellular transport

transport that occurs through cell membranes

paracellular transport

transport that occurs between cells

intravascular dosing

drug placed directly into blood (IV or IA)

intravascular dosing steps (3)

distribution, metabolism, excretion

extravascular dosing

systemic routes and regional routes

extravascular dosing steps (4)

absorption, distribution, metabolism, excretion

systemic routes

oral, SL, buccal, IM, SQ, dermal, pulmonary, rectal

regional route

ventricular and parenchymal delivery to the brain, peritoneal delivery to abdomen, pleural delivery to lungs

drug properties affecting transport across membranes

molecular size

lipophilicity

degree of protein binding

charge (degree of ionization)

cell membrane affecting transport across membranes

SA, membrane thickness, permeability characteristics

diffusion coefficient

how easily a drug diffuses through a mediumd

diffusion coefficient units

cm²/s

lipid/water partition coefficient

how lipophilic a drug is → where drug tends to be

lipid/water partition coefficient units

none

SA of membrane units

cm²

thickness of membrane units

cm

drug concentration on each side of membrane unit (C1, C2)

microgram/mL

What drugs are able to cross lipid membrane?

unbound, polar drugs

pH hypothesis (drug transport)

only unionized non polar drugs are able to cross (transcellularly)

pKa

pH at which [unionized] = [ionized]

% ionized [A-] =?

100 x [A-]/([A-]+[HA])

if acid has higher pH than pKa?

more deprotonated ions

if base has lower pH than pKa?

more protonated ions

extravasation

drug movement into tissue space from blood through either para/transcellular transport

factors determining drug distribution

perfusion rate, capillary permeability, binding in blood, binding in tissues, partitioning into fat

perfusion-rate limited transport

drug rate dependent on flow of blood

permeability-rate limited transport

drug rate dependent on movement into tissue