Metabolism and Excretion II

Question 1

Enterohepatic Recycling:

Answer 1

Drug metabolites in liver (usually conjugates that increase MW to ˃300) are secreted into bile, stored in gallbladder, delivered to intestine via bile duct, hydrolyzed by bacterial enzymes back to the parent drug (more lipid soluble) and undergo reabsorption from the gut

Question 2

Describe the therapeutic implications of enterohepatic recirculation of drugs.

Answer 2

• Reduces the elimination of the drug and prolongs its half-life and duration of action in the body.
• Some drugs have “reservoir” of recirculating drug that accounts for 20% of total drug present in the body.
• Antibiotics that reduce gut flora can decrease enteroheptaic recycling and decrease plasma drug levels and is a potential mechanism for drug-drug interaction

Question 3

To prevent infant exposure through breast milk:

Answer 3

• Desynchronize breastfeeding and peak milk/drug concentration
• Choose Medication for breastfeeding mother carefully

Question 4

Examples of desynchonizing breastfeeding and peak milk/drug concentration

Answer 4

1. Breastfeed at end of dosing interval or administer after nursing
2. Administer a dose prior to infant’s longest sleep time
3. Fat (and thus drug) content of milk: increases during feeding period

Question 5

How to choose medication for breast feeding mother carefully

Answer 5

1. Select drugs with little-no passage into breast milk
2. Drugs with rapid clearance
3. Milk is MORE acidic than plasma (5.6 vs 7.4 pH) and has tendency to accumulate basic compounds by ion trapping
4. Lipid soluble compounds= increased milk concentration
5. High protein binding= decreased milk concentration
6. Never use drugs contraindicated by American Academy of PEDS
7. Drugs that can affect milk production/secretion/ejection (through prolactin, oxytocin)