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Pharmacology ` PHARMACOLOGY—PHARMACOKINETICS ANd PHARMACOdYNAMICS Pharmacology ` PHARMACOLOGY—PHARMACOKINETICS ANd PHARMACOdYNAMICS SEcTIoN II 231

Pharmacokinetics
Bioavailability (F) Fraction of administered drug
reaching systemic circulation
unchanged. For an IV dose,
F = 100%. (F) = AUC Oral x 100
Orally: F typically < 100% due to AUC IV
incomplete absorption and first-pass Plasma concentration
x100
metabolism. Can be calculated AUC IV
from the area under the curve in
a plot of plasma concentration
over time.
AUC
Oral
Time
Volume of distribution Theoretical volume occupied by the total amount of drug in the body relative to its plasma
(V d ) concentration. Apparent V d of plasma protein–bound drugs can be altered by liver and kidney
disease ( protein binding,  V d ). Drugs may distribute in more than one compartment.
amount of drug in the body
V d =
plasma drug concentration
Vd COMPARTMENT dRUG TYPES
Low Intravascular Large/charged molecules; plasma protein bound
Medium ECF Small hydrophilic molecules
High All tissues including Small lipophilic molecules, especially if bound
fat to tissue protein
Clearance (CL) The volume of plasma cleared of drug per unit time. Clearance may be impaired with defects in
cardiac, hepatic, or renal function.
rate of elimination of drug
CL = = V d × K e (elimination constant)
plasma drug concentration
Half-life (t 1/2 ) The time required to change the amount of drug in the body by ⁄2 during elimination.
1
In first-order kinetics, a drug infused at a constant rate takes 4–5 half-lives to reach steady state. It
takes 3.3 half-lives to reach 90% of the steady-state level.
0.7 × V d
t 1/2 = in first-order elimination # of half-lives 1 2 3 4
CL
% remaining 50% 25% 12.5% 6.25%

Dosage calculations C p × V d In renal or liver disease, maintenance dose  and
Loading dose =
F loading dose is usually unchanged.
C p × CL × τ Time to steady state depends primarily on
Maintenance dose = t 1/2 and is independent of dose and dosing
F
C p = target plasma concentration at steady state frequency.
τ = dosage interval (time between doses), if not
administered continuously

FAS1_2019_05-Pharmacology.indd 231 11/7/19 4:08 PM