Lecture 4 - ADME/Pharmacokinetics II

What is distribution?

Transfer and equilibration of drug from plasma to other body locations

What three things is distribution dependent on?

1. Physiochemical properties of the drug

2. Protein binding of the drug

3. Delivery of drug to tissues

Is drug protein binding reversible?

Yes

What do acidic drugs bind to? What about basic drugs?

-Acidic drugs: bind to albumin

-Basic drugs: bind to alpha-one acid glycoprotein

How does distribution occur in the brain?

Usually reserved for highly lipid soluble drugs

What is the effective drug concentration?

Concentration of free drug at a receptor site

What is plasma drug concentration?

Rate of input of drug, distribution, and elimination

What three things are specific for each drug?

-Bioavailability

-Volume of distribution

-Clearance

What is half life (t_1/2)? What is the formula?

Time for plasma concentration of a drug to decrease by ½ concentration after a single dose

-t_1/2 = 0.693 (V_d/Cl_p)

What is the volume of distribution? What is the formula?

-How much of a single dose stays in plasma

-V_d = D/C_o (L)

What is clearance? What is the equation?

-Amount of drug from a single dose cleared from plasma per hour

-Cl_p = K_el x V_d (L/hr)

What is the oral fraction? What is the equation?

-Fraction of a single oral dose that gets to plasma

-F_oral = AUC_oral / AUC_iv 

What is the one compartment model?

-Assumes the body is a single, kinetically homogenous unit

-Distribution occurs instantaneously between blood and other body fluids

What is a first-order process?

-Rate of elimination of the drug is proportional to the amount of drug in the body at that time

-Constant fraction

What is a zero-order process?

-Nonlinear kinetics

-Constant quantity of drug is eliminated per unit of time

How many half-lives does it take to reach steady-state concentration?

5

What is the loading dose equation?

-LD = C_ss X V_d (mg)

-C_ss = concentration at steady state

What is the maintenance dose equation? 

-MD = C_ss X V_d X K_el (mg/hr or mg/min)

-MD = C_ss X Cl_p (mg/hr or mg/min)

What is the steady state?

Concentration of drug in plasma remains stable

What is the two compartment model?

Highly perfused organs and tissues have rapid distribution compared to other tissues