IV and Infusion Kinetics

Context-Sensitive Half-Time

• Much more clinically useful than elimination half-time
• The time necessary for the plasma drug concentration to decrease by 50% after discontinuing a continuous infusion of a specific duration (context refers to infusion duration)
• Computer simulations of multicompartmental pharmacokinetic models used to calculate context-sensitive half-times
• Considers distribution, metabolism as well as duration of continuous IV administration on drug pharmacokinetics

Time to Recovery

• Depends on how far the plasma concentration of a drug must decrease to reach levels compatible with awakening
• If concentration of drug is only just above the level required for awakening, time to recovery will quick

Effect-Site Equilibration Time

• The half-time of equilibration between drug concentration in the plasma and drug effect
• Short effect-site equilibration time produces more rapid onset of pharmacologic effect

Dosing Regimes

• Drug effects usually show a characteristic temporal pattern

• Lag period precedes onset of effect, after which the magnitude of the effect increases to a maximum and then declines
• Drug effect intensity is related to its concentration above a minimum effective concentration, while duration of effect reflects the length of time the drug level is above MEC
• The therapeutic window is the concentration range that provides efficacy without unacceptable toxicity

Dosing rate = target C_P . CL/F

• Where C_P is target plasma concentration, CL is clearance in L/hr, and F is the oral availability (a fraction)

Loading Dose

• A series of doses given at the onset of therapy to achieve target concentration rapidly

Loading dose = target C_P . V_ss/F

• Where V_ss is the volume of distribution