1. Excretion of drugs

2. Routes of drug excretion
Urine : it is the most important channel of excretion for most drugs
Faeces : most of the drug present in faeces are derived from bile.
Exhaled air : gases & volatile liquids ( general anaesthetics, alcohol) are eliminated by lungs, irrespective of their lipid solubility
Saliva & sweat : these are of minor importance for drug excretion. (Lithium, thiocyanates)

3. Breast Milk : suckling infant inadvertently receives the drug
Breast Milk : suckling infant inadvertently receives the drug. Most drugs enter milk by passive diffusion. More lipid soluble & less protein bound drugs cross better. Alkaline drugs are more concentrated in it since the pH of milk is lower than the plasma.
( e.g. Morphine)

4. Renal excretion
Kidney is responsible for excretion of all water soluble substances
The amount of drug &/or its metabolite present in the urine is a sum total of glomerular filtration, tubular re-absorption & tubular secretion
Glomerular filtration : all non-protein bound drug ( lipid soluble or insoluble) is filtered. GFR declines progressively after 50 years of age & is low in renal failure

5. Tubular re-absorption : this depends on lipid solubility & ionization of the drug at the urinary pH.
non-lipid soluble & highly ionized drugs are unable to be re-absorbed.
Weak bases ionize more & are less reabsorbed in acidic urine
Weak acids ionize more & are less reabsorbed in alkaline urine
This principle is utilized for facilitating elimination of drug in poisoning. E.g. urine is alkalinized in Barbiturate & salicylate poisoning. Urine is acidified in Morphine & Amphetamine poisoning

6. Tubular secretion : this is the active transport of organic acid & base substances via 2 transport mechanism.
Organic acid transport
Organic base transport
Active transport of the drug across the tubules reduces the concentration of its free form in the tubular vessels and promotes dissociation of protein bound drug, which again is secreted

7. Kinetics of elimination
Drug elimination is the sum total of metabolic inactivation & excretion
Clearance (CL) : it is the theoretical volume of plasma from which the drug is completely removed in a unit time
CL is calculated as :
CL = Rate of elimination
Plasma concentration (C)

8. First order kinetics Also known as exponential kinetics
the rate of elimination is directly proportional to the drug concentration
Here, CL remains constant
A constant fraction of the drug is eliminated in a unit time

9. Zero order kinetics Also known as linear kinetics
The rate of elimination remains constant irrespective of drug concentration
CL decreases with increase in concentration of drug
A constant amount of drug is eliminated in a unit time

10. Plasma half life
The plasma half life (t ½ ) of a drug is the time taken for its plasma concentration to be reduced to half of its original value
Plasma concentration
Time
Distribution
Elimination 10 5
t ½

11. 1st t ½ - 50% drug is eliminated
2nd t ½ - 75% ( ) drug is eliminated
3rd t ½ % ( ) drug is eliminated
4th t ½ % ( ) drug is eliminated
Thus, nearly complete drug elimination occurs in 4 – 5 half lives
For drugs eliminated by
First order kinetics – t ½ remains constant
Zero order kinetics – t ½ increases with dose because CL progressively decreases