Week 2 -Pharmacokinetics After I.V. Bolus - Urine

Question 1

Why is renal excretion important

Answer 1

• Its the MAJOR elimination mechanism for many drugs

Renal elimination includes renal excretion and renal metabolism
- excretion is of the unchanged drug (the same form drug was adminstered as, not metabolised)

Question 2

Why might we use urine data instead of plasma

Answer 2

• Can readily measure renal excretion of unchanged drug
• Can gather CLR info. (this info cant be collected from plasma data alone)

Question 3

How to calculate fraction of dose excreted unchanged (fe) from urine data following an IV bolus dose

Answer 3

fe = Ae (∞) ÷ D
fe = CLR ÷CL

• D = dose
• fe = value from 0-1
  
  • if value is closer to 1 = renal elimination is more dominant
  • if value closer to 0 = drug is elimintaed another way

Question 4

How to calculate renal clearance (ClR) from urine data following an IV bolus dose

Answer 4

CLR = Ae (∞) ÷ AUC

• Ae (∞) - the cumulative amount of unchanged drug excreted in urine
• Equation represents the max. amount of drug that can be excreted in urine
• Ae (∞) will ONLY equal D (dose) if all of the drug is renally excreted (CLR = D ÷ AUC) ~ RARE
• As conc. of drug ↑ in urine the conc. ↓ in plasma
• t1/2 = half the Ae (∞)
• CLR is a key parameter determining renal elimintaion

Question 5

Average urine excretion rate plotted against averagre plasma conc.

Answer 5

• the 2 factors are proprtional = should have a linear line (straight line) graph
  - slope of line = CLR
• measure plasma conc. at midpoint of urine collection e.g. if collect urine every 2 hrs measure plasma conc. every 1 hr
• when collecting urine sample ensure bladder is completely empty or drug still sitting in bladder will be carried over to next sample