Pharmacokinetics – ADME

Excretion

What are the factors affecting excretion of a drug?


Various routes by which drugs can be eliminated

- Most important

  • kidney
  • liver

- Less important

  • bile
  • sweat

 

Main site of drug excretion = KIDNEYS


Impaired renal function = impaired drug excretion (if drug is mainly renally excreted)

Drugs also excreted in bile, sweat, lungs, breast milk, tears, genital secretions, saliva

 

Factors affecting drug excretion

- Glomerular filtration

  • Normal GFR is about 120ml/min
  • Rate of urine production is about 1-2mL/min.
  • Drugs can be filtered at the glomerulus

 

Renal failure
- Creatinine is a substance produced in skeletal muscle which is excreted through the kidneys
- It is neither passively reabsorbed nor actively secreted
- Estimation of creatinine clearance, estimates clearance of drugs filtered at glomerulus

 

Cockcroft Gault equation

 

  • Age in years
  • Weight in kilograms
  • Serum creatinine in micromol/litre
  • Constant 1.23 for men 1.04 for women

 

Estimated Glomerular Filtration Rate – GFR

- Renal function in adults is increasingly being reported as eGFR
- eGFR uses serum creatinine, age, sex and race (for African-Caribbean patients).
- This is normalised to a body surface area of 1.73m2 and derived from a specific formula.
- Absolute GFR = eGFR x individual’s body surface area /1.73

 

Which patients will have altered renal function?

- Elderly

  • Reduced renal mass
  • Reduced renal blood flow

- Neonates

- Patients with renal impairment

  • Acute
  • Chronic

 

Table: Renal Impairment (using GFR)

 

Grade GFR Serum Creatinine
Mild 20-50ml/min 150-300 micromol/L
Moderate 10-20ml/min 300-700 micromol/L
Severe < 10ml/min > 700 micro mol/L

 

Table: Renal Impairment (using eGFR)

 

Degree of impairment eGFR mL/minute/1.73 m2
Normal - Stage 1 More than 90 (with other evidence of kidney damage)
Mild - Stage 2 60–89 (with other evidence of kidney damage)
Moderate - Stage 3 30–59
Severe - Stage 4 15–29
Established renal failure - Stage 5 Less than 15

 

Rule of thumb: Assume every elderly patient has at least mild renal impairment

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