pharmaconcepts

Useful Pharmacokinetic Concepts

plasma rapid IV bolus

After peak concentration is achieved, there are two phases- a phase (distribution phase) is characterized by a rapid decrease in plasma concentration, i.e. redistribution
b phase (elimination phase) - gradual decrease in plasma concentration due to elimination (by metabolism and excretion)

volume of plasma cleared of drug (mL/min.) by elimination (metabolism and/or excretion)
Important variable for continuous IV administration, since it influences the steady-state plasma concentration (if drug administration rate exceeds the clearance, drug will accumulate)
Drug concentration and blood flow to the organ clearing the drug are crucial considerations

Calculated value, but is a reflection of the apparent volumes of the compartments into which the drug disperses

Protein binding, a high degree of ionization, and low lipid solubility results in a small V_d (one can imagine the drug being "stuck" in the central compartment, and therefore not being able to distribute into a large volume)

the time necessary for the plasma concentration of a drug to decrease by 50% during the elimination phase
Five elimination half-times result in nearly complete elimination of the drug
Elimination half-time is only useful in a single compartment model (the central compartment/plasma)
Elimination half-times do not reliably predict the plasma drug concentration after an infusion is discontinued, simply because most drugs behave according to a multicompartment model (elimination half-time does not take into account the reservoir effect of many tissues)

the context-sensitive half-time describes the time required for the plasma drug concentration to decline by 50% after terminating an infusion
Context sensitive half-time is dependent upon infusion duration, lipophilicity of the drug, and both distribution and redistribution from central and peripheral compartments. Tissue saturation plays a key role.

typically the context-sensitive half-time increases with increased duration of infusion, HOWEVER, the behavior of a particular drug depends upon its lipid-solubility and clearance mechanisms
if clearance mechanisms are efficient (i.e. propofol) the context-sensitive half-time tends to be low

One compartment models assume that our bodies are a single compartment, i.e. the central compartment. The one compartment model is characterized by a single volume, and a single clearance of that volume. However, patients obviously have more than one compartment, and anesthetic drugs behave accordingly. Two or three compartment models are most often used to characterize the pharmacologic behavior of anesthetic drugs. These models have a single, central compartment, and the remaining compartments are peripheral. Each compartment has its own volume, and own clearance. The sum of all volumes is the volume of distribution at steady state Vd_ss. The following figure demonstrates one, two, and three compartment models.