This document discusses drug elimination kinetics. It describes the main routes of drug excretion from the body, including hepatic excretion through bile and renal excretion through glomerular filtration and tubular secretion/reabsorption. The kinetics of drug elimination are explained, including plasma half-life, repeated dosing to achieve steady state concentrations, and target level strategies using loading and maintenance doses. The principles of first-order and zero-order elimination, as well as therapeutic drug monitoring, are also outlined.

1. ELIMINATION KINETICS
Dr. Lily Dubey
Assistant Professor
Dept. of Pharmacology
Dr. D Y Patil Medical College

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3. ROUTES OF DRUG EXCRETION
 Hydrophilic compounds can be easily
excreted
 Liver
 Kidney
 Sweat and saliva
 Milk
 Pulmonary
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4. HEPATIC EXCRETION
 Drugs can be excreted in bile, especially when the are
conjugated with – glucuronic Acid
Portal
vein
Bile duct
Intestines
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5. ENTEROHEPATIC CYCLING
 Eg. steroid hormones, rifampicin, amoxycillin,
contraceptives
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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

6. RENAL EXCRETION
 Glomerular Filtration
 Depends on their plasma protein binding and renal
blood flow
 Tubular Reabsorption
 Back diffusion of Drugs (99%) – lipid soluble drugs
 Depends on pH of urine, ionization
 Tubular Secretion
 Energy dependent
 Utilized clinically – penicillin Vs probenecid, probenecid
Vs uric acid (salicylate)
 Quinidine decreases renal and biliary clearance of
digoxin by inhibiting efflux carrier P-gp
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7. KINETICS OF ELIMINATION
 Pharmacokinetics - F, V, CL, t1/2
 Clearance: volume of plasma from which drug
is completely removed in unit time
CL = Rate of elimination /C
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8. PLASMA HALF-LIFE
 Defined as time taken for its plasma concentration
to be reduced to half of its original value –
t1/2 = In2/k
In2 = natural logarithm of 2 (0.693)
k = elimination rate constant
Elimination rate constant = CL / V
t1/2 = 0.693 x V / CL
CL = RoE/C
V = dose IV/C
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9. PLASMA HALF-LIFE
1 half-life …………. 50%
2 half-lives………… 25%
3 half-lives …….…..12.5%
4 half-lives ………… 6.25%
50 + 25 + 12.5 +
6.25 = 93.75
93.75 + 3.125 +
1.56 = 98%
after 5 HL
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10. REPEATED DOSING
 At steady state, elimination = input
Dose Rate = target Cpss x CL
Oral administration
Dose rate = target Cpss x CL/F
Zero order kinetics: Michaelis Menten kinetics
RoE = (Vmax) (C) / Km + C
Vmax = max. rate of drug elimination
Km = Plasma conc at which elimination rate is half maximal
CL = Roe/C
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11. THE PLATUE 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
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12. STEADY STATE CONCENTRATION
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Peaks and troughs

13. KINETICS OF ELIMINATION
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15. KINETICS OF IV DOSING
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16. KINETICS OF ELIMINATION
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FIRST ORDER ZERO ORDER
Drug eliminated in
unit time
Constant fraction Constant amount
Nature Elimination proportional to
drug concentration
Elimination saturates at
higher concentration
Plasma
concentration – time
curve
Exponential decay Linear decay
On log scale linear Non- linear
kinetics Linear kinetics Non linear kinetics
Drugs Most drugs(95%) Alcohol, aspirin, warfarin,
theophylline

17. TARGET LEVEL STRATEGY
 Low safety margin drugs (anticonvulsants, antidepressants,
Lithium, Theophylline – maintained at certain concentration
within therapeutic range
 Drugs with short half-life (2-3 Hrs) –administered at conventional
intervals (6-12 Hrs) – fluctuations are therapeutically acceptable
 Long acting drugs:
 Loading dose: Single dose or repeated dose in quick succession –
to attain target conc. Quickly
Loading dose = target Cp X V/F
 Maintenance dose: dose to be repeated at specific intervals
Maintanace dose = ssPC X Clearance/F
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18. THERAPEUTIC DRUG MONITORING(TDM)
 Useful in
 Narrow safety margin drugs – digoxin, anticonvulsants,
antiarrhythmics and aminoglycosides
 Large individual variation – lithium and antidepressants
 Renal failure cases
 Poisoning cases
 Not useful in
 Response measurable drugs – antihypertensives
 Drugs activated in body – levodopa
 Hit and run drugs – Reseprpine, MAO inhibitors
 Irreversible action drugs – Organophosphorous compounds
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