After 5 half lives _______% of the drug is gone.

After 5 half lives **97**% of the drug is gone.

_________________

Unlikey to have any more effect

Most drugs in veterinary medicine follow _________ kinetics

Most drugs in veterinary medicine follow **First Order** kinetics

Half-life (T_{1/2}) equation

t_{1/2 }= 0.693 x Vd / Cl_{B}

When saturation occurs, Cl_{B} (increases/decreases) and t_{1/2} (increases/decreases) leading to drug accumulation and potential development of side effects.

When saturation occurs, Cl_{B} (increases/**decreases**) and t_{1/2} (**increases**/decreases) leading to drug accumulation and potential development of side effects.

T/F: Half life is dose dependent

False, it is proportional

Dosage

"Recipe" for how much to give (mg/kg)

Bioavailability % (F%) equation

F% = AUC (extravascular) / AUC (IV) x 100%

F% is equal to ________ for IV administration

F% is equal to **100** for IV administration

One Compartment Model

Consider the body as consisting of a single, homogeneous compartment. Volume would equal the volume of distribution. Model may be closed or open taking in account for clearance.

Primary compartment method by which pharmacokinetic parameters are now determined in veterinary medicine

Stochastic model

(Non-Compartmental)

Zero Order Kinetics

Amount of drug is eliminated per unit time is fixed

Peak

Highest concentration of each dose

Dose

The amount of a drug given to an individual (mg)

Time to achieve steady state levels is (dependent/independent) of dose.

Independent

What are the components of a dosage regimen

Dosage

Route of Administration

Frequency

Duration

Plasma Concentration Steady State is reached at how many half lives

5

Extent

How much the mass (dose) of a drug changes in total

Loading Dose

Single dose administered to get the plasma concentration to a certain level, to be maintained by repeated dosing

Compartment Model

Views the patient as a number of compartments, each compartment is a collection of tissues that have similar pharmacokinetics

Pharmacokinetics

Use of mathematical modelsto quantitate the time course of drug disposition in man and animals

Allometric Scaling

Uses pharmacokinetic data in multiple species to try to predict the behavior of a drug in a species for which this information is unknown

What type of pharmacokinetic model is used for drugs that follow first order kinetics?

Non-Linear Model

Clearance

Volume cleared of the drug per unit time (mL/min/kg)

What happens to plasma concentration and half life if a dose is doubled?

Plasma concentration will increase

Half life will remain the same

Population Pharmacokinetics

System estimates pharmacokinetics by looking at populations. Mathematical techniques allow studies of large numbers of animals with less individual sampling. Can allow for development of parameters for a drug that would apply to all breeds/ages/genders/etc.

Elimination roughly equals

Metabolism + Excretion

As Vd increases, t_{1/2} (increases/decreases)

Increases

Multi-Compartment Model

Consists of multiple compartments. Math gets incredibly complex

Vd Equation

Vd = Dose / C_{p}

Bioavailability (F)

Fraction of the dose given which finds its way into systemic circulation

Intermittent Dosing Cp^{ss} Equation

__ DOSE x F __= Cp^{ss} x CL_{B}

Interval

Two Compartment Model

Considers the body as consisting of two compartments; a central compartment into which the drug is added and from which it is clear and a second compartment to which the drug distributes. Graphical representation shows a distribution and elimination phase.

Dose_{CRI} Equation

= Cp^{ss} x CL_{B}

As Clearance increases, t_{1/2} (increases/decreases)

Decreases

Trough

Lowest concentration of each dose

Describe the pattern of Plasma Concentration of a drug in relation to Plasma Elimination of a drug

Plasma concentration will follow the same pattern as plasma elimination, only upside down

________________________

1 half life - 50% of final Cp^{ss}

5 half lives - Cp^{ss} will be 97% of eventual steady state

Apparent Volume of Distribution (Vd)

Theoretical volume a drug would occupy if it was evenly distriuted through the body at the same concentration as in plasma

First Order Kinetics

Proportion of drug eliminated per unit time is fixed

Elimination Rate Constant

Fraction/ Proportion of the drug that would be eliminated per unit time

Volume of Distribution (Vd)

Volume of drug would occupy if it was evenly distributed at the same concentration as in plasma (L/kg)

Very high Vd ( > L/kg ) suggests that a drug is

Very high Vd ( > L/kg ) suggests that a drug is **distributing preferentially to tissue and may even be sequestered somewhere**

Total Body Clearance (CL_{B})

Volume of distribution of drug in body cleared of teh drug per unit time (mL/min/kg) and this is the sum of clearance by the kidneys, liver and everywhere else.

____________________

Takes into account both metabolism and excretion

Bioavailability (F) equation

F = AUC ( extravascular ) / AUC (IV)

Very low Vd suggests that a drug is

Very low Vd suggests that a drug is **not being distributed to all of the tissues**

After 2 half lives _______% of the drug is gone.

After 2 half lives **75**% of the drug is gone.

Bioequivalence

Different formulations of the same drug have the same drug bioequivalence when they are absorbed to a similar extent and similar rate

Stochastic Model

(Non-Compartmental)

Involve using analysis of large numbers of actual animal data (time-plasma curves).

Elimination Half Life

Time required for the drug concentration to decrease by one half or 50%

Rate

How fast the mass (dose) of a drug changes per unit time (mg/min)

Bioavilability is a measure of

Bioavilability is a measure of ** drug exposure**

What measurements are important to compare in bioequivalence

AUC

C_{max}

T_{max}

Mean Resistance Time (MRT)

Used in the non compartment model, describes the length of drug persistence in the body

Plasma Concentration at Steady State Cp^{ss}

Concentration at which the amount of drug going in is equal to the amount going out

After 3.3 half lives _______% of the drug is gone.

After 3.3 half lives **~90**% of the drug is gone.