EXCRETION

Organs of Excretion
• Excretion is a transport procedure which the prototype
drug (or parent drug) or other metabolic products are
excreted through excretion organ or secretion organ
• Hydrophilic compounds can be easily excreted.
• Routes of drug excretion
1. Kidney
2. Biliary Sweat saliva
3. Milk
4. Pulmonary
Hepatic Excretion

• Drugs can be excreted inbile, especially when the

are conjugated with – glucuronic Acid
• Drug is absorbed glucuronidated or sulfatated
in the liver and secreted through the bile
glucuronic acid/sulfate is cleaved off by bacteria
• In GI tract drug is reabsorbed (steroid
Hormones, rifampicin, amoxycillin, contraceptives)
• Anthraquinone,heavy metals – directly excreted in
colon
Renal Excretion
• Glomerular Filtration
• Tubular Reabsorption
• Tubular Secretion
Glomerular Filtration
• Normal GFR – 120 ml/min
• Glomerular capillaries have pores larger than usual
• The kidney is responsible for excreting of all water
soluble substances
• All nonprotein bound drugs (lipid soluble or insoluble)
presented to the glomerulus are filtered
• Glomerular filtration of drugs depends on their plasma
protein binding and renal blood flow - Protein bound
drugs are not filtered !
• Renal failure and aged persons
Tubular Re-absorption
• Back diffusion of Drugs (99%) – lipid soluble drugs Depends on
pH of urine, ionization etc.
• Lipid insoluble ionized drugs excreted as it is – aminoglycoside
(amikacin, gentamicin, tobramycin)
• Changes in urinary pH can change the excretion pattern of
drugs
• Weak bases ionize more and are less reabsorbed in acidic urine.
• Weak acids ionized more and are less reabsorbed in alkaline
urine
• Utilized clinically in salicylate and barbiturate poisoning –
alkanized urine (Drugs with pKa: 5 – 8)
• Acidified urine – atropine and morphine etc.
Tubular Secretion
• Energy dependent active transport – reduces the free
concentration of drugs – further, more drug dissociation
from plasma binding – again more secretion (protein
binding is facilitatory for excretion for some drugs)
• OATP – organic acid transport OCT – organic base
transport P-gp
• Bidirectional transport – Blood Vs tubular fluid
• Utilized clinically – penicillin Vs probenecid, probenecid Vs
uric acid (salicylate)
• Quinidine decreases renal and biliary clearance of digoxin
by inhibiting efflux carrier P-gp
Renal Excretion
Acidic urine
• alkaline drugs eliminated acid drugs reabsorbed
Alkaline urine
• acid drugs eliminated
• alkaline drugs absorbed
Kinetics of Elimination
• Pharmacokinetics - F, V and CL
• Clearance: The clearance (CL) of a drug is the
theoretical volume of plasma from which drug is
completely removed in unit time
• CL = Rate of elimination (RoE)/C
• Example = If a drug has 20 mcg/ml and RoE is 100
mcg/min
• CL = 100/20 = 5 ml /min
• First Order Kinetics (exponential): Rate of
elimination is directly proportional to drug
concentration, CL remaining constant
• Constant fraction of drug is eliminated per unit time
• Zero Order kinetics (linear): The rate of elimination
remains constant irrespective of drug concentration
• CL decreases with increase in concentration
Alcohol, theophyline, tolbutmide etc.
Zero Order 1st Order
Plasma half-life
• Defined as time taken for its plasma concentration
to be reduced to half of its original value – 2 phases
rapid declining and slow declining
• t1/2 = In2/k
• In2 = natural logarithm of 2 (0.693) k = elimination
rate constant = CL / V t1/2 = 0.693 x V / CL

CL = RoE/C

V = dose IV/C
Excretion - The Plateau
Principle
• Repeated dosing:
• When constant dose
of a drug is repeated
before the expiry of 4
half-life – peak
concentration is
achieved after certain
interval
• Balances between
dose administered
and dose interval
Monitoring of Plasma
concentration
• Useful in
• Narrow safety margin drugs – digoxin, anticonvulsants,
antiarrhythmics and aminoglycosides etc
• Large individual variation – lithium and antidepressants Renal
failure cases
• Poisoning cases
• Not useful in
• Response mesurable drugs – antihypertensives, diuretics etc
Drugs activated in body – levodopa
• Hit and run drugs – Reseprpine, MAO inhibitors Irreversible
action drugs – Orgnophosphorous compounds
Prolongation of Drug action
• By prolonging absorption from the site of action –
Oral and parenteral
• By increasing plasma protein binding
• By retarding rate of metabolism
• By retarding renal excretion