Pharmacokinetics I & II - Issar

Question 1

Zero-order kinetics

Answer 1

• Reaction proceeds at a constant rate
• Ex: Ethanol
• Non-linear pharmacokinetics

Question 2

First-order kinetics

Answer 2

• Reaction proceeds at rate dependent on drug concentration

* Linear pharmacokinetics

Question 3

Mixed order kinetics

Answer 3

• Switches from zero order to first order

Question 4

What is a compartment model?

Answer 4

• Kinetics in the body simplified to represent compartments which communicate with each other
• Characteristics
o Uniform distribution of drug within each compartment
o Within compartment drugs are well-stirred (mixed up completely)
o Rate constants represent drug entry or exit
o Open system

Question 5

One-compartment model

Answer 5

• Single well-mixed container
• Linear model
• Drug achieves instantaneous distribution throughout the body
• Drug equilibrates instantaneously between tissues
*Not implying that the drug concentration in plasma is equal to drug concentration in tissues

Question 6

Two-compartment model

Answer 6

• Central compartment and peripheral compartment
o Think organs and skin
o Central compartment tissues are highly perfused
o Peripheral compartment tissues are less well-perfused
• Rates
o K12 = movement from central → peripheral
o K21 = movement from peripheral → central
• NO instantaneous distribution

Question 7

Calculating IV dose

Answer 7

• Use Vd formula and then correct for salt using salt factor

* Dose/Salt

Question 8

Clearance

Answer 8

• Represents entire body as drug elimination system = Cl total
• Cl total = Cl renal + Cl liver + Cl liver
• Kelim = (Cl total)/Vd
• Clearance and Vd are NOT dependent on each other
o A change in one will not cause a change in the other
o If they both change it’s because something is affecting both of them, not them affecting each other
• Kelim is related to half-life

Question 9

What are the units for Area Under the Curve (AUC)?

Answer 9

ug.hr/mL

Question 10

Half-life

Answer 10

• Plasma HL = Elim HL = biological HL
• Time taken for plasma conc drug to decrease by 50%
• Fraction of drug eliminated during each interval is constant
• ONLY valid for First-order kinetics
o Can’t calculate half-life for zero-order
• Inversely proportional with clearance

Question 11

What are the factors influencing half-life?

Answer 11

1. Changes in distribution/metabolism/excretion
2. Alkaline urine lowers half-life of weak acids
3. The young and elderly
4. Half life is shortened by a decrease in Vd and an increase in Cl
5. Half-life is inversely proportional with Cl
6. But directly proportional with Vd
7. Dose does not affect half-life
   Strong plasma protein binding increases half-life

Question 12

Describe a single IV bolus dose using the two-compartment model

Answer 12

• Large dose given at one time
• CENTRAL – peripheral
• Central – peripheral
• Central - PERIPHERAL

Question 13

IV Infusion

Answer 13

• Same dose given over a long time
• Initially, conc is rising because the load is not high enough yet
o Elim rate «< Infusion rate

Question 14

Loading dose

Answer 14

• Loading dose = target concentration x Vd

* Longer half-life → longer time to accumulate to steady state compared to a shorter half-life drug

Question 15

Accumulation period

Answer 15

Concentration builds up with increased doses in order to overcome half-life

Question 16

Multiple dosing

Answer 16

• At least some of the previous dose remains resulting in a cumulative effect
o Eventually rate of input = rate of output
o Then accumulation no longer takes place and you reach a steady state

Question 17

What is the dosage interval?

Answer 17

• Dosage interval = amount of time in which you take 1 dose

o Ex: 1 tab every 8 hours → a dosage interval of 8

Question 18

What are the factors that affect fluctuation?

Answer 18

1. Half-life
• Has biggest effect
• Short half-life produces more fluctuations than drugs with slower elimination
2. Dose division
3. Dosage form

Question 19

How can you restrict fluctuation?

Answer 19

• Shorter intervals (ex: 4x/day)

* Use a sustained release formula

Question 20

Dose division

Answer 20

• Frequent dosing
o Run into noncompliance
• Greater individual doses
o Run into greater fluctuations

Question 21

Slow release formulations

Answer 21

Peaks that are delayed and lower shorter period of decline