Useful revision guide

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Useful revision guide Instant Clinical
Pharmacology E.J. Begg Useful information on
individual drugs (although a bit old now) Basic
Clinical Pharmacokinetics (2nd Edition) M.E.
Winter
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• Drug dosing
• Important factors
• concentration of drug in plasma
• rate of drug elimination
• rate of drug absorption

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Therapeutic window
Toxic level
Minimum therapeutic level
Cp
time
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Revision of pharmacokinetic terms 1st
order elimination rate of elimination depends on
plasma concentration C C0e-kt (k rate
constant of elimination) Half life (t1/2) time
for plasma concentration to fall by 50 Zero
order elimination (pseudo zero order) rate of
elimination is constant and independent of plasma
concentration
Plasma Concn (Cp)
zero
1st
time
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Zero order elimination Half life varies with
concentration
Plasma Concn (Cp)
time
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Volume of distribution (Vd) Vd
dose C0 Volume of water in which a drug would
have to be distributed to give its plasma
concentration at time zero. Can be larger than
total body volume frusemide 7
litres aspirin 14 litres propranolol 273
litres digitoxin 38 liters 4 ml min-1
digoxin 640 litres 130ml min -1 Plasma
clearance (ClP) volume of blood cleared of its
drug content in unit time CP ClM ClR ClB
.
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Bioavailability (F) measure of the amount of drug
absorbed into the general circulation Area under
the curve (AUC) obtained from the plasma
concentration v time plot gives a measure of the
amount of drug absorbed Foral
AUCoral AUCiv
Clearance F. dose AUC
iv
Cp
oral
time
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• Same drug, same dose different formulation
• different amounts absorbed
• different peak concentration
• different AUCs

Cp
time
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Therapeutic window
Same drug, same route, different doses
Toxic level
Minimum therapeutic level
Cp
time
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Different rates of absorption (different routes
of administration) Assume the bioavailability is
the same (i.e. 1 for all routes)

• Slower the rate of absorption
• time to peak longer
• amplitude of peak is less
• longer drug in body

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Two compartment model
tissues
plasma
elimination
Redistribution elimination
Plasma Concn (Cp)
e.g. thiopentone
elimination
time
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Intravenous infusion
At steady state rate of infusion rate of
elimination Css.Clearance
Css (plateau)
Cp
C Css(1- e-kt)
Time to 90 of Css 4 t1/2
time
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Half life hours steady state
Lignocaine 2 8 hours Valproate 6 24
hours Digoxin 32 6 days Digitoxin 161 28
days
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Rising phase of the infusion curve is governed
by the rate of elimination
Height of plateau is governed by the rate of
infusion
2X mg min-1
Cp
X mg min-1
time
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Dosing interval
MTL
Cp
time
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Multiple dosing
At Steady State amount administered amount
eliminated between doses
Cavss
Cp
Rising phase of the curve is still governed by
the rate of elimination
time
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Loading dose(s)
Loading dose Cpeak . Volume of distribution
Cp
time
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Tetracycline t1/2 8 hours 500mg loading dose
followed by 250mg every 8 hours
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Cavss F . Dose Clearance. T
T dosing interval
Cavss
Reducing the dose AND reducing the interval Cavss
remains the same but fluctuation in Cp is less
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• Altered pharmacokinetic profile
• liver metabolism
• Disease
• Pharmacogenetics (cytochrome P450 polymorphisms)
• renal impairment
• Disease
• Elderly