Chap 3 Pharmacokinetics Flashcards
(40 cards)
Volume of distribution (apparent)
The ratio of the amount of drug in the body to the drug concentration in the plasma or blood. Units: liters
Clearance
The ratio of the rate of elimination of a drug to the concentration of the drug in the plasma or blood. Units: volume/time, eg, mL/min or L/h
Half-life
The time required for the amount of drug in the body or blood to fall by 50%. For drugs eliminated by first-order kinetics, this number is a constant regardless of the concentration. Units: time
Bioavailability
The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation
Area under the curve (AUC)
The graphic area under a plot of drug concentration versus time after a single dose or during a single dosing interval. Units: concentration × time; eg, mg min/mL
Peak and trough concentrations
The maximum and minimum drug concentrations achieved during repeated dosing cycles
Minimum effective concentration (MEC)
The plasma drug concentration below which a patient’s response is too small for clinical benefit
First-pass effect, presystemic elimination
The elimination of drug that occurs after administration but before it enters the systemic circulation (eg, during passage through the gut wall, portal circulation, or liver for an orally administered drug)
Steady state
In pharmacokinetics, the condition in which the average total amount of drug in the body does not change over multiple dosing cycles (ie, the condition in which the rate of drug elimination equals the rate of administration)
Biodisposition
Often used as a synonym for pharmacokinetics;
-the processes of drug absorption, distribution, and elimination.
Sometimes used more narrowly to describe elimination
The effective drug concentration is the concentration of a drug at the _______
receptor site
(Vd)
apparent volume of distribution (Vd)
(CL)
clearance (CL)
The volume of distribution (Vd) relates the amount of _____ to the ____ according to the following equation:
drug in the body
plasma concentration
Vd= Amount of drug in the body
Plasma drug concentration (Units =Volume)
Clearance equation
Clearance (CL) relates the rate of elimination to the plasma concentration:
CL= Rate of elimination of drug (divided) by Plasma drug Concentration
Units: Volume per unit time
Note: For a drug eliminated with first-order kinetics, clearance is a constant;
CLerence depends of what factors
Clearance depends on the drug, blood flow, and the condition of the organs of elimination in the patient.
Most drugs in clinical use obey the first-order kinetics rule described in the text.
Name 3 important drugs that do not?
- ethanol
- aspirin
- phenytoin
What is 1/2 life
Half-life (t 1/2) is a derived parameter, completely determined by Vd and CL.
Like clearance, half-life is a constant for drugs that follow first-order kinetics.
Half-life can be determined graphically from a plot of the blood level versus time
1/2 life equation
t 1/2 = 0.693×Vd
CL (Units = Time)
bioavailability
Note:
bioavailability of a drug is the fraction (F) of the adminis- tered dose that reaches the systemic circulation
Note: bioavailability is generally reduced by incomplete absorption (and in the intestine, expulsion of drug by intestinal transporters), first-pass metabolism, and any distribution into other tissues
The area under the curve (AUC)
Graph
The area under the curve (AUC) is used to calculate the bioavailability of a drug. The AUC can be derived from either single- dose studies (left) or multiple-dose measurements (right). Bioavailability is calculated from AUC(route)/AUC(IV).
The oral route of administration is the most likely to have a large first-pass effect and therefore low bioavailability. What tissues contribute to this effect?
The oral route of administration entails passage of the drug through the gastric and intestinal contents, the epithelium and other tissues of the intestinal wall, the portal blood, and the liver before it enters the systemic circulation for distribution to the body. Metabolism by enzymes in any of these tissues, expul- sion by drug transporters, and excretion into the bile all may contribute to the first-pass effect of oral administration.
Maintenance Dosage
Equation:
Note:
Because the maintenance rate of drug administration is equal to the rate of elimination at steady state (this is the definition of steady state), the maintenance dosage is a function of clearance
Equation:
Dosing rate = CL × Desired plasma concentratition Bioavailability
Note: If it is important to maintain a concentration above the mini- mum therapeutic level at all times, either a larger dose is given at long intervals or smaller doses at more frequent intervals
Loading Dose equation:
note:
Loading dose = Vd × Desired plasma concentration Bioavailability
Note:
clearance does not enter into this computation. If the loading dose is large (Vd much larger than blood volume), the dose should be given slowly to prevent toxicity due to excessively high plasma levels during the distribution phase.
