Lecture 32 Flashcards
What are the three factors that affect plasma concentration of drug?
rate of input of drug into plasma
rate of distribution of drug
rate of elimination
a measure of the apparent space in the body availabe to contain the drug
Volume of distribution
a measure of body’s ability to eliminate the drug
clearance
the fraction of drug absorbed into the systemic circulation
bioavailability
What does low Vd mean?
higher drug concentration in plasma than amount of drug in extravascular system (tissue)
What does high Vd mean?
higher drug concentration in the body (extravascular system) than drug concentration in plasma
Equation for Vd
Vd=Dose/C0
Equation for Dose
Dose = Vd * TC (target plasma drug concentration)
Equation for clearance
CL = Rate of elimination of drug / plasma drug concentration
For a drug eliminated with first-order kinetics, CL is constant, thus the ratio of the rate of elimination to the plasma concentration is the same regardless of plasma concentration. Why is it?
Because physiological mechanisms of drug elimination are not saturated
Why is half-life important?
It determines the rate at which blood concentration rises during a constant infusion and falls after infusion is stopped.
What is steady-state concentration?
Point where amount administrated per unit time is equal to amount eliminated per unit time
For first-order, how many half lives does it take to reach steady state?
4 half lives
Half life equation
Half life = (0.693*Vd) / CL
For first order, what is the relationship between infusion rate and Css?
Doubling the infusion rate doubles Css, but increasing infusion rate does not influence the time required to reach Css, it still take 4 half lives
Factors increasing half life (7) and decreasing half life (1)
incresasing
- obesity & pathologic fluid (effects on Vd)
- ageing, CYP inhibition, cardiac, liver, renal failure (effect on CL)
Decreasing
- CYP induction
When is nonlinear kinetics observed?
When drug concentration exceeds Km (zero order)
Drugs that exhibit zero order elimination (saturation kinetics) (3)
aspirin at high doses
ethanol
phenytoin
Rate of elimination equation for zero order
Drug concentration is much higher than Km (so remove Km)
Rate of elimination = V max
Properties of saturation kinetics (zero order)
- rate of elimination is maximal and independent of drug concentration
- a constant amount of drug is eliminated per unit time
(for first order, a fraction of drug is eliminated) - plot of plasma concentration vs time is linear.
- CL is not constant, varies with the concentration of drug.
- Half life is not constant
Equation for CL in zero order
CL = V max / (Km +C)
