1.4 Fundamental PK Calculations

dose →

absorption → central compartment → metabolism (liver) or excretion (kidney)

metabolism & excretion

1^o order kinetics

zero order kinetics

enterohepatic recycling

drug → stomach → portal vein → liver → kidney (excretion) or bile system

renal filtration

glomerular filtration, tubular secretion, tubular reabsorption

bioavailability

fraction of an administered drug dose that reaches the systemic circulation unchanged

-significant in clinical assessment of dosing and establishes equivalence of products

bioavailability calculation

calculated by comparing AUCs of drug administered by a route of interest to a reference AUC

absolute BA

reference AUC is IV

relative BA

reference BA is another dosage form or route of administration

trapezoidal rule

area of segment = ((h₁ + h₂)/2) x length = ((c₁ + c₂)/2) x (t₂ - t₁)

clearance

rate of drug removal

-measurement of volume of plasma from which a drug is completely removed per unit time

-perfusion ↑, clearance ↑

first order disappearance of drug (bolus)

apparent volume of distribution (V_D)

V_D = D/C_P⁰

total clearance

Cl_T = k * V_D; k is time^-1

noncompartmental: Cl_T = dose/AUC (mass/vol*time)

half life

time it takes for plasma concentration to decrease by half

t_1/2 = 0.693/k

C_max and T_max

maximum plasma concentration and time to reach maximum plasma conc

steady state

when drug loss per day = drug intake per day