L5 - Introductory Pharmacokinetics Flashcards
Volume of Distribution (Vd) =
Proportionality constant demonstrating volume drug would have to be dissolved in, in order to achive same concentration of drug in plasma
decreases in heart disease, increases in liver disease
Vd = Dose / Cp
Ke =
Elimination rate constant
Fraction of the total amount of drug in the body that is eliminated per unit time
Rate of Elimination =
RoE = Ke . A
A = total Amount of drug in body
t1/2 =
Half-life
t1/2 = 0.693 / Ke
or
t1/2 = (0.693 . Vd) / CL
Plasma drug concentration at given Time (Ct) =
Ct = C0 (0.5)^n
Ct = Cp at a time C0 = Cp at 'time zero' ie start, eg after infusion ends or IV bolus given
Clearance (CL) =
volume of plasma cleared of drug per unit time
Determines maintenance dose rate
RoE = CL x CP
and because RoE = Ke . A
can be rearranged:
CL = Ke . Vd
Css =
Rate of administration = rate of elimination
Css is eliminated by first order kinetics after infusion/ maintenance oral dose stops.
Thus,
Css is technically time zero (C0)
Ct = Css (0.5)^n when it is being eliminated
Ct = Css (1 - 0.5^n) when it is being infused
Cpss = maintenance dose rate / CL
IV Bolus
Loading dose to get to Css essentially
number of half-lives =
n = t / (t1/2) t = time
CpSS and dose Rate
Cpss = maintenance dose rate / CL
How many Half-lives to reach Css?
Approximately 5
What determines time to reach Css?
t1/2, NOT infusion rate
Calculating Css for Oral Administration =
Css (avg) = (F . dose) / (Cl . dose interval)
F = fractional oral bioavailability
Fractional oral bioavailability (F) =
F = AUC (oral) / AUC (IV)
AUC = area under curve
usually in mg.h/L
Assessing Bioequivalence
Chemical equivalence - drug products contain same amount of active component
Bioequivalence - drug, when given to same patient at same dose, result in equivalent Cp
Theraputic Equivalence - drug, when given to same patient at same dose, result in equivalent theraputic and adverse affects
