Bioavailibility (Pharmacokinetics)

Question 1

What is Bioavailability?

Answer 1

IV administration means the entire dose reaches the systemic circulation, i.e. 100% bioavailability (F)
Bioavailability will be lower via other routes
Can depend upon permeability of the biological membrane, drug properties,and other route-dependent factors, e.g. stomach contents for oral route

Question 2

F =

Answer 2

fraction of administered dose of drug which reaches system circulation (intact)

Question 3

First-pass (presystematic) metabolism

Answer 3

Drugs absorbed from the stomach, small intestines and upper colon pass into the hepatic portal system  liver

Some drugs are metabolised extensively through their “first-pass” through the liver

Presystematic metabolism is one factor which contributes to bioavailability

Question 4

What is Naloxone used for?

Answer 4

Used to combat opiate overdose
Rapid onset required
Undergoes first pass metabolism

Question 5

How is bioavailability determined?

Answer 5

Absolute bioavailability (F) is calculated by comparing the amount absorbed by one route, e.g. oral, to the i.v. route

Most commonly derived through the production of blood plasma concentration – time curves after i.v. and oral dosing

Samples of blood withdrawn from a patient/volunteer at time intervals after a dose is administered

The same patient would have boththe i.v. and oral dose administered(at different times – “washout” period)

Comparison is the made of the “area under the curve”

Question 6

In this example the AUCoral is roughly half that of AUCiv

Answer 6

bioavailability of the oral formulation is therefore 0.5 (50%)

The reduced bioavailability may be due to incomplete absorption and/or first-pass clearance

This would be repeated with several different patients/volunteers

Question 7

what is the equation for bioavolibility?

Answer 7

F = AUCoral / AUC

Question 8

What if it’s not possible to give thesame dose by the i.v. and the oralroutes?

Answer 8

We can add in a factor to correct for the dose:

F = AUC oral Dose i.v. / AUC i.v. Dose oral

Question 9

Finding the AUC following an i.v. bolus dose
[GRAPH]

Answer 9

Area of a trapezoid = 0.5 (a + b) h

Where a & b are the two parallel sides and h the distance between them

Question 10

Relative bioavailability

Answer 10

Sometimes it may not be possible to administer a drug via the i.v. route
Relative bioavailability (Frel) is calculated by comparing the amount absorbed from a test formulation, e.g. an oral drug solution, to a standard formulation such as a tablet

Question 11

F rel

Answer 11

often used to measure changes in formulation parameters, e.g. dosage form, excipients, processes

Question 12

F rel equation

Answer 12

F rel - AUC test / AUC standard

Question 13

What is Bioequivalence?

Answer 13

Relative bioavailability is used to evaluate bioequivalence (BE) of two products containing the same drug

BE studies are important when a generic equivalent of an innovator product is launched
Pharmacokinetic studies to assess BE will investigate parameters such as AUC, Cmax and Tmax

Question 14

Salt factor (S) or salt correction factor?

Answer 14

the fraction of the dose (which may be in the form of a salt or ester) that is the active drug
The salt / ester does not contribute to the therapeutic effect
Antibiotic erythromycin has a MW of 733.9 Da
Salts and esters erythromycin are also used pharmaceutically
Ethyl succinate (862.1)
Stearate (1018.4)
Lactobionate (1092.2)
Estolate (1056.4)
Multiply bioavailability (F) by S to get true value

S = 733.9 / 862.1 = 0.851