Proportional to: elimination rate constant and the volume of distribution

Meaning: as the rate of elimination goes up, the amount of clearance goes up

as the volume of drug increases, the more clearance a drug has

Rate of elimination = kel*Vd*Cp

Proportional to: clearance, concentration of drug in the plasma, volume of distribution, and the elimination rate constant

As rate of elimination goes up, more drug is cleared

Dependent on t 1/2, CL, and Vd

Proportional to: CL

Inversely proportional to: t1/2 and Vd

A higher rate constant for elimination gives more clearance. The longer it takes a drug to reach it’s half life (bigger half life), the smaller the rate constant for elimination.

The larger the Vd, the smaller the rate constant for elimination

Whne log(Cp) is plotted vs. time

Proportional to: Clearance

Inversely proportional to: volume of distribution

The larger rate constant for elimination, the faster the clearance (more steep the slope)

The larger the volume of drug, the smaller the rate constant for elimination (less steep slope)

**Remember, kel = Vd/CL

The larger the rate constant for elimination, shorter the half-life

The larger the clearance value, the shorter the half life

The larger the volume of drug the longer the half-life

Dependent on drug, bioavailability, and the initial concentration in the plasma

Proportional to: dose and bioavailability

Inverse proportional to: initial concentration of drug in the plasma

As the bioavailability increases, the volume of drug increases

As the dose increases, the volume of drug increases

As the initial concentration of drug in the plasma increases, the volume of drug decreases

Inversely proportional to: CL

realize: % = 2^-t

if t = 2t1/2, 25% of the drug is remaining

if t = 4t1/2,

Proportional to: urinary flow and Concentration in the urine

As urinary flow and the concentration of drug in the urine increase, the rate of renal excretion/elimination go up

The renal clearance = urinary flow

Generally, the higher the concentration in the urine and the lower the concentration in the plasma, the higher the clearance

As urinary flow increases the clearance rate increases

When Cu+Cp, the renal clearance is only dependent/=to urinary flow

CLtotal = CLren +CLmet + CLother

Includes renal clearance, metabolism clearance, and other clearnance

There is no t1/2

The rate of elimination is not dependent on concentration; it is CONSTANT

CL is not a defined constant

CL is dependent on concentration and dose

When an enzyme is at maximal capacity

When drugs are in very high concentration

dose dependent

capacity-limited

At higher substrate concentrations, the enzyme becomes saturated and cannot be act as fast

At the top is 0 order with no 1/2 life and as reaction proceeds it shows first order kinetics, where a half life is shown

The 2 graphs are broken at the point of Km

Looks like a linear direct plot with slope = Vmax

Looks like an exponential decay

At 0 order (top) there is an exponential decay (Cp>Km)

At 1st order (bottom) there is a linear slope; slope = -kel (Cp

slope = -kel = -CL/Vd = (-Vmax/KmVd)

2 exponential decays, first representing 0 order is not often important when determining the pharmacokinetics

Elimination phase determined by looking at the bottom half of the graph (the first order kinetics)

Rate of administration = rate of elimination

Also the fluctuations of Cp in dosing interval

Dependent on: maintenance does (Dm), bioavailability (f), and the amount of time (delta t)

Proportional to: Dm and F

Inversely proportional to: amount of time

**??

If this is true what is the equation for steady state?

Dm*F/delta t = CL*Ctarget

ULTIMATELY::

Dm=CL*Ctarget*delta t/F

CL

Rate of elimination

delta t = dosing interval

Proportional to: Dm and bioavailability

Inversely proportional to: Clearance

Seen with drugs that have a narrow therapeutic window and become toxic

Makes it hard to determine maintenance dose

takes a lot of doses to get to steady state (Ctarget)

shows smaller difference between Cmax and Cmin

takes much less dosings to get to steady state (C target)

shows much bigger difference between Cmax and Cmin

Proportional to: target concentration and volume of drug

Inversely proportional to: bioavailability

The higher the target concentration, the higher the loading dose

The higher the volume of drug, the higher the loading dose

The higher the bioavailability, the lower the loading dose **because you don’t need as much drug to give you a good effect