Pharmacokinetics 1

Question 1

what is Clinical pharmacokinetics?

Answer 1

Applying pharmacokinetic data to design safe and effective therapeutic regimens for an individual patient

Question 2

1) what is Bioavailability?

2) how do we measure the drug concentration in plasma?

Answer 2

1) the fraction of an administered dose that reaches the bloodstream
2) drug concentration in the plasma: take blood from patient, centrifuge out the blood cells, use HPLC to measure drug conc. in plasma
- shown on a graph with Cp (drug conc in plasma) over time.

Question 3

outline how we determine how much drug in a given dose was absorbed?

Answer 3

1) Do Cp vs t measurement for a dose of drug administered by: (a) By IV injection and (b) Orally (or any other relevant route)
2) Calculate the area under the curve (AUC) for the two resultant “CP versus t” curves
3) Compare AUC values to get the amount absorbed

Question 4

what is Absolute bioavailability and what is the formula?

Answer 4

1) Assess bioavailability of a formulation relative to intravenous (IV) route.
2) F route= AUC route / AUC IV

Question 5

We tend to assume that drug is absorbed into plasma, but some gets into lymph system & elsewhere. describe where else drugs distribute in the body

Answer 5

1) distributes to tissues, including the site of action.

2) Some drugs act directly on blood e.g. warfarin

Question 6

name the two commonly used models for distribution

Answer 6

1) The one compartment model

2) The two compartment model

Question 7

describe the one compartment model for distribution

Answer 7

1) The assumption is that drug is distributed throughout the body in a single homogeneous compartment
- ABSORPTION→ [COMPARTMENT] →ELIMINATION
2) The compartment is purely imaginary, but can be said to “equate to” blood, plus various highly perfused tissues such as heart, liver, lungs

Question 8

describe the two compartment model for distribution

Answer 8

1) Assumes that drug is distributed in two compartments

                     [Peripheral Compartment]
                               ↕ equilibrates  -Absorption → [central compartment] →elimination

2) The compartments are purely imaginary , but the central can be said to “equate to” highly perfused tissues and the peripheral to other tissues such as fat, muscle, skin.

Question 9

1) define the term volume of distribution (Vd)
2) give the formula for Vd
3) calculate the Vd for the following: 100mg of drug in the body. Cp measured = 10mg / L

Answer 9

1) A term that relates plasma drug concentrations to the total amount of drug present in the body
2) Vd = mass of drug in the body /drug concentration in plasma (Cp)
3) 10 Litres
- (In the case of IV injection, the mass of drug in the body is simply the dose)

Question 10

what is the formula for Cp?

Answer 10

Cp = mass of drug in the body / Vd

Question 11

1) one use of Vd is to calculate loading dose. what is the equation used to calculate loading dose?
2) how do you know how much drug to give for a loading dose?

Answer 11

1) loading dose = Cp x Vd
2) look up what is the desired Cp for the drug is and then
Look up the apparent Vd for the drug in a book.

Question 12

calculate the loading dose: desired Cp is 0.1 mg/ml ; Vd = 5L.

Answer 12

1) loading dose = Cp x Vd

2) Loading dose = 5,000 ml x 0.1 mg/mL = 500 mg

Question 13

what is the rate of change for a zero order process?

Answer 13

1) the rate of change is CONSTANT

2) straight line on a graph

Question 14

1) what equation can be used for any drug that undergoes zero order elimination to work out what its concentration will be at anytime in the future?
2) why is this equation important?

Answer 14

1) Cpt = Cpₒ - Kₒt (REMEMBER)
- if you know what the concentration of the drug is at time zero, and you know the elimination rate constant; you can work out the concentration of the drug at any point in the future
2) this help us to work out when the patient will need the next dose to keep the drug at therapeutic concentrations in the body

Question 15

the equation Cpt = Cpₒ - Kₒt can be switched over to plot a straight line as zero order processes are constant. Cpt = - Kₒt + Cpₒ is the same as y= mx + c.
why would you plot this graph?

Answer 15

gives us direct access to the elimination rate constant if the data is unavailable in a book or if the drug is new

Question 16

what is the rate of elimination of a first order process?

Answer 16

the rate of elimination is NOT constant, it changes with time
2) the vast majority of drugs undergo first order elimination

Question 17

what equation would you use for any drug that is eliminated by first order to work out what its concentration will be at anytime in the future?

Answer 17

Cpt = Cpₒ exp ¯ᴷ₁ᵗ

Question 18

The first order equation Cpt = Cpₒ exp ¯ᴷ1ᵗ , can be really difficult to work with because it has exponentials . state the easier to deal with logarithmic form of the equation.

Answer 18

ln Cpt = In Cpₒ −K₁t (REMEMBER)

Question 19

what time of elimination is occurring if ln(Cp) vs t plot is a straight line?

Answer 19

1) So if a ln(Cp) vs t plot is a straight line, then the drug is undergoing first order elimination and we can get the rate constant and the drug concentration in the plasma at time zero