Pharmacokinetics of Parenterals

Question 1

What are the different orders written as?

Answer 1

• zero: k
• first: kC
• second: kC²

Question 2

What occurs before after Cmax?

Answer 2

before: absorption
after: distibution (drug leaving blood circ) and elimination

Question 3

What is duration in terms of PK graph?

Answer 3

time spent above MEC

Question 4

What is the simplest PK model?

Answer 4

IV bolus

initial dose known

distribution and elimination only

one compartment - distibution negligible

starts at C_max , goes down - only elimination

Question 5

Why does IV admin have no absorption phase?

Answer 5

• 100% bioavailability
• no FPM
• directly into blood circ

Question 6

What will the initial conc after administration of IV bolus depend on?

Answer 6

• initial dose
• V_d
  
  • affected by lipophilicity and protein binding
  • if Vd large; plasma conc is low and theres a longer half life

Question 7

Why do hydrophilic drugs have a lower Vd?

Answer 7

less likely to come out of blood and pass membrane

Question 8

How do you calculate initial conc of a IV bolus admin?

Answer 8

dose/ V_d

Question 9

What order of kinetics will most drugs follow after IV bolus?

Answer 9

first order elimination

-dC_p / dt = -kC

or

C = C₀e^-kt

Question 10

What is the basic formula for total clearance?

Answer 10

Cl_total = Cl_renal + Cl_hepatic + Cl_other

other: lung/sweat

Question 11

How does half life link to clearance?

Answer 11

t_1/2 = ln2/k

k_e = Cl_t/V_d

Question 12

What is the steady state of IV bolus administration?

Answer 12

state in which drug plasma conc is constant within range

Question 13

Why is the dosing interval included in steady state equation?

Answer 13

takes into consideration the fact that the drug may not be 100% eliminated before next dose

Question 14

When may a loading dose not be given?

Answer 14

if theres a risk of toxicity

Question 15

How can you determine if C_{s average} is appropriate?

Answer 15

if its outside of TW its not appropriate

Question 16

What parameters are equal at C_ss?

Answer 16

infusion = elimintation

Question 17

What is wash in and wash out in terms of first order kinetics?

Answer 17

wash in: infusion > elimination

wash out: elimination > infusion (stopped)

Question 18

What are limitations to infrequent large IV doses and frequent small doses?

Answer 18

infrequent large IV doses: outside of TW

frequent small doses: takes a few doses to get within TW

Question 19

What parenteral formulations have the quickest onset of action and why? Go down in decreasing order.

Answer 19

1. aqueous solution - already in solution
2. aqueous suspension - has a dissolution phase
3. oil based solution - consider lipophilicity of drug and affinity for formulation
4. oil based suspension: has a dissolution phase and consider lipophilicity of drug and affinity for formulation

Question 20

When is it considered that C_ss is reached?

Answer 20

when Cp is within 5% of the true Css

direct relationship between C_ss and Q (rate of infusion) but time needed to reach C_ss is independent of Q

Question 21

Whats the relationship between helf life and steady state?

Answer 21

long half life = days to reach steady state; consider a loading dose

short half life = steady state reached within hours

Question 22

When would a first order graph give a straight line?

Answer 22

when plotted as semi-log conc