138 - Advanced Pharmacokinetics

Question 1

Basic aspects of pharmacokinetics

Answer 1

ADME Administration, absorption, distribution, metabolism, excretion

Question 2

Equation describing renal clearance of drug

Answer 2

(drug concIN - drug concOUT)/drug concIN * blood flow Extraction ratio x blood flow

Question 3

Renal clearance

Answer 3

Amount of blood from which drug is removed by kidneys per time (EG mL/minute) GFT + TS - TR

Question 4

Maximal GFR

Answer 4

120mL/min

Question 5

Maximal CLrenal

Answer 5

800mL/min

Question 6

CL

Answer 6

Rate of elimination/concentration of drug

Question 7

CLtotal

Answer 7

CLrenal + CLhepatic + CLother (CLtotal is additive)

Question 8

Normal relationship between drug concentration in blood and elimination

Answer 8

Normally the higher the blood concentration, the greater the rate of elimination (first order elimination)

Question 9

Simplest way to administer drug (pharmacologically)

Answer 9

IV injection

Question 10

Distribution equilibrium

Answer 10

When drug behaves in the body as if it is in a single compartment

Question 11

Elimination rate constant

Answer 11

NOT ELIMINATION RATE. Is a constant that affects rate of elimination, in conjunction with the concentration of drug in the body

Question 12

Relationship between drug concentration in the body with time after administration

Answer 12

Exponential decline in concentration

Question 13

Features of rapid IV administration with first order elimination 1 2 a 3 a

Answer 13

• Rapid rise • Drug has half life – Time taken for concentration to fall by 1/2 • Peak concentration (Cpeak) related to dose (X0) and Vd - Cpeak ~= X0/Vd

Question 14

Short term i.v. infusion with rapid distribution and first order elimination 1 2 3 4 5

Answer 14

• K0 (infusion rate) - KX • K0 is rate at which new bolus is administered. • rate of accumulation decreases as concentration increases • peak not as high as for i.v.bolus • after infusion over, get elimination only (simple first order)

Question 15

Common K0 for rapid infusion

Answer 15

Every half hour to a few hours

Question 16

What are rapid infusions useful for?

Answer 16

Useful for drugs that show toxicity at concentration not much greater than concentration that produces therapeutic effect

Question 17

*Appearance of graph of rapid infusion

Answer 17

Question 18

*Appearance of a graph of long term IV infusion

Answer 18

Question 19

What is steady-state concentration relative to?

Answer 19

K0/(VdK), eg K0/clearance rate Proportional to rate at which drug is cleared. The more quickly it is cleared, the lower the steady state concentration

Question 20

Features of long term i.v. infusion with one compartment model and first order elimination 1 2 a

Answer 20

• At steady state, rate of infusion = rate of elimination • Css is proportional to infusion rate – easy to dial up a particular concentration

Question 21

With long term i.v. infusion with one compartment model and first order elimination, what does rate of infusion equal

Answer 21

Rate of elimination at steady state

Question 22

*Long term IV dosing versus multiple dosing

Answer 22

Question 23

How often are most drugs given with multiple dosing regimes?

Answer 23

Every half life of drug. Gives a 2x difference between peak and trough of drug concentration at steady state.

Question 24

Number of half-lives required for getting to steady state with multiple doses

Answer 24

~7 half lives

Question 25

When might a loading dose be needed with a multiple-dosing regime?

Answer 25

If the patient needs to get to steady state very quickly, EG heart failure, antimicrobials for sepsis.

Question 26

How is a loading dose administered?

Answer 26

Give loading dose to get concentration to roughly steady state, then continue infusion as you would with a normal multiple dose regime

Question 27

How is a loading dose calculated?

Answer 27

Using volume of distribution

Question 28

Process by which most orally-administered drugs are absorbed in GIT

Answer 28

Lipid solubility, crosses cell membranes (lipid diffusion). Some drugs can be actively-transported, but this is uncommon.

Question 29

Oral administration with one compartment model and first order elimination

Answer 29

dX/dT = KaXa - KX Xa = amount of drug at absorption site eg. in small intestine Ka = absorption rate constant Rate of change of drug in body (dX/dT) is related to absorption rate and elimination rate

Question 30

Features of oral administration with one compartment model and first order elimination 1 2 3

Answer 30

• Peak not as high as with i.v. – Some elimination during absorption plus • Not all drug might be absorbed • Some drug might undergo first pass hepatic metabolism

Question 31

How can bioavailability be calculated?

Answer 31

AUCoral/AUCiv x 100 = bioavailability. AUC = amount of blood in bloodstream (area under curve, referring to an integral of concentration/time graph)

Question 32

Types of injected administration routes that have a similar concentration/time curve to oral administration

Answer 32

Intramuscular, subcutaneous