see also:

• pharmacokinetics

• The main routes of drug excretion are:
  • 1. urine;
  • 2. faeces;
  • 3. expired air (volatiles);

• 1. Glomerular filtration:
  • rate drug enters filtrate depends on MW & plasma conc.
  • binding to plasma protein retards filtration;
• 2. Tubular secretion:
  • cells of prox. convoluted tubules actively secrete by:
    • 1. glucose transport;
    • 2. amino acid transport;
    • 3. anion transport;
    • 4. cation transport;
  • the active transport may remove drugs bound to albumin if the affinity for transport system is sufficient;
  • there may be competition for the transport system, for example, penicillin & probenecid; thiazides et al & uric acid;
• 3. Tubular reabsorption:
  • distal tubular reabsorption may occur by:
    • 1. passive diffusion of nonionized lipid soluble drugs as considerable conc. gradient develops as the urine becomes more concentrated;
      • thus, acid urine increases reabs. of acids, this is especially so for acids pKa 3-8, & bases pKa 6-11;
      • eg. aspirin is cleared 80x faster in alkaline urine!
    • 2. specific transport systems (less important);

• the volume of plasma that would contain the amount of drug appearing in the extrarenal urine per unit time:
  • Clearance = (conc. in urine) x (urine output rate) / (concentration in plasma)
• Clearance Ratio:
  • ratio of clearance to either inulin clearance or GFR, if >1,
  • implies tubular secretion; if <1, implies tub. reabsorption;
• Elimination Constant (Kelim) for drugs only excreted by urine:
  • Kelim = Renal Clearance / Vd

• if drug is largely excreted by urine, then dosage rate must be reduced to avoid accumulation;

• 1. Passive diffusion as previously discussed, but in addition if albumin is lost into gut, then bound drugs travel with it;
• 2. Active transport (mainly via bile):
  • 3 main transport systems, similar to renal prox. tubules but more efficient for lipid soluble drugs:
    • 1. anions;
    • 2. cations;
    • 3. nonionized:
      • cardiac glycosides;
  • If reabsorbed then enterohepatic shunt!

• The main factors governing elimination by this route are the same as those for uptake:
  • 1. conc. in alveolar gas & plasma;
  • 2. blood/gas partition coefficient;