Excretion Flashcards
Kidney Functions (3)
- Glomerular Filtration
- Tubular Secretion
- Tubular Reabsorption
Passive Kidney Functions
Glomerular Filtration & Tubular Reasborption
Active Kidney Function
Tubular Secretion
Rate of Excretion
Rate of Filtration + Rate of Secretion - Rate of Absorption
Glomerular Filtration
- Plasma water is filtered at a rate ~125 mL/min and is called GFR
- ONLY unbound drug is filtered
Rate of Filtration
=GFR * Cu
=GFR * C * fp
Rate of Excretion
If a drug is ONLY filtered and is ALL excreted in urine
=Rate of filtration (GFR * C *fp)
Renal Clearance (Clr)
Clr = Rate of Excretion/ C
=GFR * fp
Measurement of GFR
- Creatinine (endogenous) and insulin (exogenous)
- not bound, secreted, reabsorbed
- Clr for these compounds approximates GFR (fp = 1)
Secretion
- Carrier mediated, active transport
- Similar equation to hepatic metabolism
Clr,sec
Qr * [ (fp * Cli,sec) / Qr + fp * Cli,sec)]
Clr, total (assuming no reabsorption)
= Clr,filt + Clr,sec (assume NO absorption)
Reabsorption depends on…
- Urine pH (Ionization)
- Urine flow - increased urine flow will decrease the time for reabsorption, therefore more rapid excretion
- Lipophilicty/hydrophilicity
True Clr,total
= (Clr,filt + Clr,sec)(1-fraction reabsorbed)
How do we know if a drug is reabsorbed?
Clr,total < Clr,filt
Acidic Drugs + Urine pH
- Polar acids - not reabsorbed, extensive excretion
- Nonpolar, strong acids with pKa < 6- mostly ionized, little reabsorption, extensive excretion
- Nonpolar, weak acids with pKa > 12 - mostly unionized, extensive reabsorption, little excretion
- Nonpolar acids with pKa 6-12 - Varying degress of ionization, reabsorption, and excretion
Basic Drugs + Urine pH
- Polar bases - not reabsorbed, extensive excretion
- Nonpolar, strong bases with pKa > 12 - mostly ionized, little reabsorption, extensive excretion
- Nonpolar, weak bases with pKa < 6 - mostly unionized, extensive reabsorption, little excretion
- Nonpolar bases with pKa 6-12 - carying degrees of ionization, reabsorption, and excretion
Forced Diuresis
- More rapid elimination is a way of detoxifying a patient with a drug overdose
- Control pH as well as flow change
- Goal is to increase ionization, decrease reabsorption, and increase excretion
Criteria for Forced Diuresis
- Drug is eliminated mainly by renal pathway
2. Drug must be normally extensively reabsorbed from the renal tubules
Problems collecting VALID urinary excretion data… (5)
- Significant fraction of unchanged drug must be excreted in urine
- Good assay selectivity
- Frequent sampling
- Sufficiently long sampling time (5-7 half lives required for 95 and 99% elimination, respectively)
- If possible, urine flow and urinary pH should be monitored (hard when out patient)
K =
ke + knr
dXu/dt
= keDose * e^(-Kt)
ln(dXu/dt)
= ln(keDose) - Kt
**When plotting, use midpoint for sampling time
Xu
= (keDose/K)*(1-e^(-Kt))
XuINF
= keDose/K
ln(XuINF - Xu)
ln(XuINF) - Kt
-Gives slope of -K
XuINF - Xu
-Term commonly called the AMOUNT of drug REMAINING to be EXCRETED (A.R.E)
Biliary Excretion
-Important for the excretion of bile and drugs
MW + Excretion
- < 300 = excreted almost exclusively in the urine
- 300 – 500 = excreted both in the urine and bile
- > 500 = excreted mainly in the bile
Polarity + Excretion
- Excretion into bile requires a strong polar group
- Many metabolites are excreted in the bile (Glucoronidation – increases polarity and increases molecular weight by 200)
Enterohepatic Circulation + Excretion
- Drug (or metabolite) that is secreted into the bile from the liver is expelled into the duodenum with gall bladder contraction via common bile duct
- Parent drug may be reabsorbed and become systemically available (or excreted in feces)
- Glucoronide conjugates can be hydrolyzed back to the parent compound by intestinal β-glucoronidase enzymes
Multiple Doses + Excretion
- More drug is secreted into bile after multiple doses or a large, singular dose
- Can affect the elimination and absorption rates
Hepatic Excretion Peaks
- Peak 1 - normal oral absorption peak as drug is absorbed from the gut
- Peak 2 - biliary reabsorption
