Factors Affecting ADME

Question 1

Renal excretion

Answer 1

Overall elimination of drugs is the net effect of glomerular filtration, tubular secretion and tubular reabsorption

Factors affecting rate of elimination:

• Integrity of the kidney
• Molecule size
• Urine flow
• Urine pH
• Kidney capacity

Question 2

Active transporters

Answer 2

OAT = transports anions 
OCT= transports cations 

Transporters are usually inducible

Only free drug can be transported across the membrane

These factors effect the rate of elimination and the therapeutic window

Question 3

Probenecid

Answer 3

A drug that binds to transporters (anion channel blocker)

This protects the kidney from CS-lyase effects of halogenated alkanes/alkenes and forces them to be excreted by the liver

It is beneficial for more toxic compounds to be excreted by the liver because it can regenerate easily

Question 4

Urine flow

Answer 4

As urine flow increases, rate of drug elimination also increases

Increasing fluid intake / using a diuretic increases drug elimination

Question 5

Liver excretion

Answer 5

The liver is the route of excretion for drugs not eliminated by the kidney

This usually includes lipophilic drugs, high molecular weight drugs and glucuronidated drugs

Question 6

Enterohepatic circulation

Answer 6

Reabsorption of drugs can also take place at the liver

As a metabolised drug passes through the GI tract, some bacteria may ‘undo’ glucuronidation, causing the drug to become active again

So, liver excretion can sometimes be unpredictable

Question 7

Factors affecting absorption

Answer 7

• The formulation (wrapping) of a drug dictates its release
• Food in the stomach generally decreases absorption, although light food can increase absorption
• Gastric motility
• Gastric pH
• GI tract integrity

Question 8

Other factors affecting ADME

Answer 8

• Age
• Gender
• Nutrition & diet
• Disease
• Drug-drug interactions

Question 9

Pharmaceutical interactions

Answer 9

There may be interactions between other synthetic drugs

Rifampicin (TB treatment) displaces NNTIs (AIDs treatment) from albumin, leading to potentially toxic levels of NNTIs in the blood

Question 10

Consumer drug interactions

Answer 10

Consumer drugs are not regulated and hence will not be standardised

St. John’s Wort and warfarin are metabolised by the same enzyme

Question 11

Food-drug interactions

Answer 11

Some foodstuffs can cause adverse reactions

Grapefruit juice interacts with terfenadine, leading to heart attacks

Question 12

P-glycoprotein

Answer 12

Pgp is an active transporter that pumps drugs back into the GI tract

Genetic variations of this protein can alter drug transport

CC = high Pgp activity 
CT = moderate Pgp activity 
TT = low Pgp activity