Module 6 Pharmacokinetics Flashcards
Clinical Pharmacokinetics
- Relationship between drug effects & concentration
- Quantitative relationship between dose & effect
- Framework for measurements of drug concentration within body fluids
Drug Disposition Parameters
- Clearance, efficiency of elimination
- Volume of distribution (apparent space)
- Elimination of half life (rate of removal)
- Bioavailability (fraction in systematic circulation)
Drug Therapy Goal
- Fluctuations & steady state within therapeutic range
Measuring Concentrations
- Site of action most accurate, not possible
- Mostly measured in plasma
Benefits of Plasma Measurement
- Non-invasive
- Correlation between plasma, therapeutic & toxic effects
Free Drug Measuring
- Elicit pharmacological response
- Theoretically would be ideal from dosing, difficult
Plasma Measuring
- Measuring plasma provides enough information
- Guide dosing
- Free + protein bound usually measured
Oral Admin Time Curve
- Absorbed into blood
- Beginning, absorption rate > elimination rate
- Later, absorption = elimination (Cmax)
- After Cmax, elimination > absorption rate
Plasma Concentration Curve
- High enough to have therapeutic effects
- Not high enough to induce toxicity
Minimum Effective Concentration (MEC)
- Perform therapeutic effect
- Drugs below level have no effect
Duration
- Length of time drug concentration above MEC
Toxic Concentration
- Plasma concentrations exceed therapeutic range
Therapeutic Range
- Above MEC, below toxic concentration
- Goal attain concentrations in range
Therapeutic Range/Window Width
- Index of usage safety
Narrow Range
- Difficult to administer
- Small effective window
- Therapeutic monitoring, ensure concentrations in target range
- Monitor through trough blood sample
Onset of Action
- Lag time varies between different administration methods
- Rate & extent of absorption impact onset
- How soon drug effects occur
Oral Onset of Action
- Lag time before MEC
Continuous Intravenous Infusion
- Rate of entry stays constant
- No absorption, drug enters systemic circulation
- Plasma concentration rises
- Elimination rate = infusion rate
- Steady state (no change plasma levels)
IV Bolus
- Rapid injection into blood
- Quick distribution
- eliminated over time
- Rate of elimination dependant on blood concentration
Repeated Dosing
- Accumulation until plateau reached (steady state)
- High level, peak
- Low level, trough
Steady State
- Peak & trough concentrations same between doses
Reducing Fluctuations
- Continuous IV infusion
- Depot preparations
- Change dosing interval
Continuous IV Infusion Characteristics
- Constant drug levels
- No peaks/troughs
- Not a feasible method
Depot Preparations
- Release drug at slow, constant rate
- Minimizes peaks/troughs
Changing of Dose Intervals
- Same total daily dose
- Multiple times throughout day
- Reduce peaks/troughs
Clearance (Cl)
- Efficiency of irreversible elimination
- Volume of blood cleared per time unit
- Route of elimination
Total Clearance
- Sum of all elimination rates
- Determines dosage rate required to maintain concentration
Dosing Rate Equation
= plasma conc x clearance
Half Life (t1/2)
- Time to decrease plasma drug conc to 50%
- Determine time to reach steady state
- Time for decline in levels after administration
Half Life Equation
= (0.693xVd) / Cl
Time to Steady State
- 5 half lives (same drug repeatedly)
Constant Dose
- Time to reach steady state independent
- Size effects steady state concentration
Loading Dose
- Given if too long to reach steady state
- Large loading doses given to quickly acclimate patient
- Smaller maintenance doses follow to keep steady state
Loading Dose Equation
= target drug conc x Vd
- Assuming 100% bioavailability
Decline from Steady State
- Time for plasma conc to decline from steady state
- Independent of the dose
- 5 half lives = 97% eliminated
- 9 half lives = 100% eliminated
