Lecture 6 Flashcards
What is “extent of absorption”?
The total amount of drug entering the body. It is not time dependent.
What is “rate of absorption”?
How quickly the drug enters the body. The rate typically changes with time.
What is the extent of absorption described as?
It is described as bioavailability. It can be considered into t2 parts:
- Fraction of drug absorbed across the gut wall (f).
- First pass extraction (ER).
Describe fraction absorbed (in terms of extent [F])?
The amount of drug that gets across the gut wall. Getting he drug from the intestine into the portal vein. Need to consider:
1. Physiocehmistry: theophylline is 100% absorbed (small, unionised - not metabolised in gut wall);
gentamicin is
Describe first pass extraction (ER) (in terms of extent [F])?
Drugs that are given orally. They drug is removed while passing through the liver; thus doesn’t reach the systemic circulation. The extraction ratio that it is getting removed by the liver is known as ER. ER is related to liver blood flow and organ clearance. Morphine has a clearance of 60% and ethanol (10-70%).
What is the formula for extent?
F = f x ( 1 - ER ).
e.g. Morphine:
F = 1 x (1 - 0.6) = 0.4
What is the overall extent known as?
The bioavailability. It can be calculated from the product of fraction absorbed across the gut (f) and the hepatic extraction ratio (ER). It is the fraction of administered dose that reaches the systemic circulation.
Describe input processes?
The rate of absorption is characterised by 3 different processes:
- Bolus e.g. intra-venous injection.
- Zero-order e.g. constant rate IV infusion.
- First-order e.g. intra-muscular injection.
Describe zero-order rate?
If you are in a fasting state, the emptying rate of the stomach is approximately constant. Drug going into the body goes out at a constant rate. The rate limiting step is the emptying rate of the stomach. Pharmaceutical control allows the slow release formulation where drugs break down at a constant rate.
Describe first-order rate?
Intestinal absorption is first-order (KA) - drug is absorbed across the intestine. Some drugs are absorbed rapidly other drugs take longer to get absorbed. the rate of absorption depends on:
1) the amount of drugs in the gut at a particular point.
2) first order rate constant (KA) - related to half life.
Absorption half life = 0.7/KA.
What are the clinical applications of absorption?
What happens if you have someone on an IV medications and you want to continue it orally - IV/oral dose conversion. Substitution of generic medicines, generic medicines are cheaper than the original product, drug regulators use the rate and extent of absorption to judge if a generic drug is bio-equivalent to the originator product.
Describe the IV/Oral Dose conversion?
IV dosage/bio-avialability (F).
e.g. Digoxin has a bioavailability of 67% and an IV dose of 500micrograms - 500/0.67 = 750micrograms.
Describe half life?
Half-life describes first-order processes. First-order processes are also called an exponential because an exponential function can be used to predict the time course of a first-order process.
What is the formula of half-life?
T1/2 = 0.7 x V / CL. This si the time for the drug concentration to fall to half of its initial value.
Describe elimination and accumulation?
After one half-life a drug will be 50% eliminated. If a drug is administered by constant rate it will accumulate to 50% of the steady state value after one half-life. After 4 half-lives we have eliminated roughly 94% of the drug.
