Pharmacokinetics of injected drugs
Compartment model (single compartment)
Central compartment contains
- Intravascular fluid
- Highly perfused tissues
* including lungs, heart (5%), brain (15%), kidney (24%), and liver (28-30%)
Intercompartmental transfer may be decreased in elderly even with same dosage and Vd
Assumptions
- All drugs are eliminated from central compartment
--> False
* e.g. atracurium and cisatracurium are eliminated differently (via Hoffman elimination and ester hydrolysis)
- Pharmacological effects of a drug parallels its plasma concentration
--> False
* e.g. cisatracurium plasma concentration is falling after 1 min, but effect is increasing
NB:
- Elimination half-time is only useful in single compartment model, but not in multicompartmental models.
Half-time and half-life
Terminology
Elimination half-time vs elimination half-life
Elimination half-time
Elimination half-time is time necessary for plasma concentration of a drug to fall to 50% during the elimination phase
- ... is independent of the dose administered
- Does not include the effect of redistribution
Elimination half-life
Elimination half-life is time necessary to eliminate 50% of the drug from the body after an IV bolus
Difference arise between half-time and half-life
Where elimination from body doesn't parallel the plasma concentration
--> elimination half-time and half-life differ
Context-sensitive half-time
Context-sensitive half-time is time necessary for plasma concentration of a drug to fall to 50% after a continuous infusion of a specific duration
- Context refers to the duration
- Context-sensitive half-time generally increases with the duration of infusion
* Due to less capacity available in inactive tissues for redistribution
- No constant relationship to elimination half-time
Effect-site equilibration time
Effect-site equilibration time is the half-time of equilibration between the drug concentration in plasma and the drug effect
--> Impacts on the time of onset
Examples of short effect-site equilibration time
- Remifentanil
- Alfentanil
- Thiopentone
- Propofol
Examples of longer effect-site equilibration time
- Fentanyl
- Sufentanil
- Midazolam
