Clinical Applications of pharmacokinetics 08 15 2014

Question 1

Absorption follows what type of kinetics?

Answer 1

Zero-roder because it does not change with time – in regards to entry rate.

Question 2

What is the relationship between the rate of infusion of the drug and the value of Css?

Answer 2

Ro= Css

If you double Ro; then you double Css

Question 3

How long does it take after starting an IV infusion to achieve that Css (steady state plasma concentration) value?

Answer 3

4 half- lives

Question 4

What does steady state plasma concentration depend on?

Answer 4

HALF-LIFE

Question 5

Chronic dose regimen:

Answer 5

Take into consideration:

1. Half life
2. therapeutic index

• start with twice the effective dose (2 x ED50)
  
  • loading dose
• repeat ED every half-life of the drug
• only works for drugs that
  1. half life is convenient (8- 24 hrs)
  2. Therapeutic is greater than 2

Question 6

Maintenance dose

Answer 6

it replaces amount of drug lost within the dosing interval (t*).

Question 7

Steady state IV dosing rate:

Answer 7

rate desired for a target plasma concentration:

Dosing rate = Rate of elimination
= CL x TC (target concentration)

Question 8

Steady state dosing rate and maintenance dose for oral drug:

Answer 8

Dosin rate need only be adjusted for the oral bioavailability of the drug

Dosing rate = (CL x TC) / Bioavailability

Maintenance dose=
= (Dosing rate / % bioavailability) x t*

Question 9

Drug accumulation factor definition?

Answer 9

How much drug is in the body at steady state relative to the amount that is given

• determined solely by (half- life / t*)
  means…
  1. if we give doses at an interval shorter than half-life, then drug will accumulate

2. If we give doses at intervals longer than half life, the drug will not accumulate!

Question 10

What are the two possible scenarios of Drug accumulation factor?

Answer 10

1. High Ra (drug accumulation factor) ratio – Half-life&raquo_space; t*
   - Long half-life
   - time to SS is long
   - Fluctuations in Css are SMALL
   - termed accumulative
2. Low Ra ratio – Half-life «< t*
   - short half life
   - time to SS is short
   - fluctuations are LARGE
   - if toxicity occurs, it ends rapidly

Question 11

basic premises for modification of dosage regimens for patients with renal disease

Answer 11

1. Sensitivity to drug is unchanged
   
   • plasma concentration of drug that produces the desired effect is the same as in normal patients
2. Elimination is impaired
   
   • kd decresaes and therefore half life is larger.
     -recall :
     CL= Kd x Vd
     half-life = 0.7 / Kd)

Question 12

Relationship between renal component of drug clearance and creatinine clearance?

Answer 12

linear relationship

renal component of drug clearance declines linearly with a decline in creatinine clearance.

Question 13

Relationship between dose and renal failure

Answer 13

Since sensitivity of drug is unchanged, if the half-life increases by half, then you have to reduce dose by half OR double the dosing interval.