Pharmacokinetics Flashcards
What is oral bioavailability of a drug?
Fraction or orally administered drug that reaches the systemic circulation.
What are some factors that affect the Oral Bioavailability of a drug?
Poor absorption in the gut
Breakdown of drug in the gut
First pass effect
What is the first pass effect in relation to absorption of drugs
When drugs are absorbed from the gut, they are taken to the liver via the hepatic portal vein to be metabolised.
Some drugs are completely metabolised in the liver therefore bioavailability is bad.
What are the factors that effect absorption of a drug across a membrane?
Lipid solubility - if highly lipid soluble the drug will easily diffuse across membrane.
pH/pKa - pH of solution and pKa of drug influence ionised/unionised ratio of drug
> The more unionised, easier diffusion across membrane
Will a weak acid like aspirin (pka 3.5) be mainly unionised or ionised in a the stomach where the pH is 3?
Mainly unionised - therefore it will easily cross the membrane
What is the Henderson Hasselbach equation for a weak acid?
pH = pKa + log [A-}/[HA]
ionised/unionised
What is the henderson hasselbach equation for a weak base?
pH = pKa + log [HA/A-}
unionised/ionised
What does the overall extent of distribution of a drug in the body depend on?
Lipid solubility (pKA/pH)
Plasma protein affinity - increased affinity for plasma proteins will be less likely to leave blood.
What is the main factor in the rate of distribution of a drug in the body?
Rate of blood flow to tissues/organs.
How can we measure drug distribution?
Vd- Volume of distribution expressed as volume or volume/mass.
Cp - plasma concentration
Vd= Amount of drug in body/plasma concentration.
What are the uses of Vd?
Partly determines plasma half life (t0.5) of a drug.
What is Volume of distribution
Volume of water in which drug would have to be distributed to give its plasma concentration.
What is clearance?
volume of plasma cleared of drug per unit time
Cl = [rate of elimination]/[Cp]
Why is clearance a useful measure ?
Because rate of elimination of most drugs varies with Cp. However clearance stays fairly constant.
What could be some situations where clearance could change?
Liver/renal disease
What is first order elimination?
Constant fraction of drug eliminated per unit time, t0.5 stays constant.
Clearance is not changing but the rate of elimination depends on how much drug is present and the higher the Cp the faster the rate of elimination.
What is zero order elimination?
Constant amount of drug eliminated per unit time
Rate of elimination stays constant.
t0.5 can vary.
What is the equation to work out t0.5 for first order elimination.
t0.5 = 0.693Vd/ Clearance
length of time that a drug persists in the blood is determined by both Vd and Clearance.
The equation says that if a drug has a high Vd then the t0.5 will be higher - it will take longer for concentration in blood to half.
The equation also shows that if the rate of clearance decreases then the t0.5 will also increase.
How can we calculate rate of elimination for intravenous infusion?
Rate of elimination = Css x Cl
CSS = concentration at which rate of infusion = rate of elimination
Time to reach CSS does not vary depending on the infusion rate.
How do we calculate CSS for oral dosing?
D = individual dose
F = oral bioavailability
T = time interval between doses in minutes
Cl = clearance
Css = D (individual dose) x F(oral bioavailability) / T (minutes between dose) x Cl. (clearance)
How do we calculate clearance?
Clearance = [rate of elimination] / [Cp]
How do we calculate intravenous infusion rate?
Rate of elimination = Cp x Cl.
As cp rises rate of infusion rises untill it is equal to the rate of elimination (CSS) ; therefore we can write the equation as ;
Rate of elimination = Css x Cl.
And as at Css Rate of elimination = Rate of infusion we can write the above equation as
Rate of infusion = Css x Cl.
Time taken to reach CSS is independant of rate of infusion/=.
What type of drugs are generally excreted by the kidney?
Drugs which are not lipid soluble
What are the 3 methods of renal excretion?
Glomerular filtration
Active secretion into nephron
Passive Reabsorption (all lipid soluble substances reabsorbed so non excreted in urine).
