Pharmacokinetics I & II - Issar Flashcards
Zero-order kinetics
- Reaction proceeds at a constant rate
- Ex: Ethanol
- Non-linear pharmacokinetics
First-order kinetics
- Reaction proceeds at rate dependent on drug concentration
* Linear pharmacokinetics
Mixed order kinetics
• Switches from zero order to first order
What is a compartment model?
• 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
One-compartment model
• 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
Two-compartment model
• 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
Calculating IV dose
- Use Vd formula and then correct for salt using salt factor
* Dose/Salt
Clearance
• 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
What are the units for Area Under the Curve (AUC)?
ug.hr/mL
Half-life
• 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
What are the factors influencing half-life?
- Changes in distribution/metabolism/excretion
- Alkaline urine lowers half-life of weak acids
- The young and elderly
- Half life is shortened by a decrease in Vd and an increase in Cl
- Half-life is inversely proportional with Cl
- But directly proportional with Vd
- Dose does not affect half-life
Strong plasma protein binding increases half-life
Describe a single IV bolus dose using the two-compartment model
- Large dose given at one time
- CENTRAL – peripheral
- Central – peripheral
- Central - PERIPHERAL
IV Infusion
• Same dose given over a long time
• Initially, conc is rising because the load is not high enough yet
o Elim rate «< Infusion rate
Loading dose
- Loading dose = target concentration x Vd
* Longer half-life → longer time to accumulate to steady state compared to a shorter half-life drug
Accumulation period
Concentration builds up with increased doses in order to overcome half-life
Multiple dosing
• 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
What is the dosage interval?
• Dosage interval = amount of time in which you take 1 dose
o Ex: 1 tab every 8 hours → a dosage interval of 8
What are the factors that affect fluctuation?
1. Half-life • Has biggest effect • Short half-life produces more fluctuations than drugs with slower elimination 2. Dose division 3. Dosage form
How can you restrict fluctuation?
- Shorter intervals (ex: 4x/day)
* Use a sustained release formula
Dose division
• Frequent dosing
o Run into noncompliance
• Greater individual doses
o Run into greater fluctuations
Slow release formulations
Peaks that are delayed and lower shorter period of decline
