IV and Infusion Kinetics

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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
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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

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  • 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 CP . CL/F
  • Where CP 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 CP . Vss/F
  • Where Vss is the volume of distribution