1. Instant Clinical Pharmacology E.J. Begg
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

2. Drug dosing Important factors concentration of drug in plasma
rate of drug elimination
rate of drug absorption

3. Therapeutic window
Toxic level
Minimum
therapeutic level Cp
time

4. 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

5. Zero order elimination
Half life varies with concentration
Plasma
Concn
(Cp)
time

6. 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 + …….

7. Area under the curve (AUC)
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 iv
Clearance = F. dose
AUC Cp
oral
time

8. Same drug, same dose different formulation
different amounts absorbed
different peak concentration
different AUCs Cp
time

9. Therapeutic window Same drug, same route, different doses Toxic level
Minimum
therapeutic level Cp
time

10. Different rates of absorption (different routes of administration)
Assume the bioavailability is the same (i.e. 1 for all routes) iv sc
oral Cp
time
Slower the rate of absorption
time to peak longer
amplitude of peak is less
longer drug in body

11. Two compartment model tissues plasma elimination e.g. thiopentone
Redistribution + elimination
Plasma
Concn
(Cp)
e.g. thiopentone
elimination
time

12. Intravenous infusion C = Css(1- e-kt) 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

13. Half life hours steady state
Lignocaine hours
Valproate hours
Digoxin days
Digitoxin days

14. 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

15. Dosing interval
MTL Cp
time

16. 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

17. Loading dose(s)
Loading dose = Cpeak . Volume of distribution Cp
time

18. Tetracycline t1/2 = 8 hours
500mg loading dose followed by 250mg every 8 hours

19. Reducing the dose AND reducing the interval
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

20. that have a low therapeutic index
Drug plasma concentration monitoring is helpful for drugs
that have a low therapeutic index
that are not metabolized to active metabolites
whose concentration is not predictable from the dose
whose concentration relates well to either the therapeutic effect
or the toxic effect, and preferably both
that are often taken in overdose

21. For which specific drugs is drug concentration monitoring helpful?
The important drugs are:
aminoglycoside antibiotics (plasma or serum)
ciclosporin (whole blood)
digoxin and digitoxin (plasma or serum)
lithium (serum)
phenytoin (plasma or serum)
theophylline (plasma or serum)
paracetamol and salicylate (overdose) (plasma or serum).
Other drugs are sometimes measured:
anticonvulsants other than phenytoin (eg carbamazepine, valproate)
tricyclic antidepressants (especially nortriptyline)
anti-arrhythmic drugs (eg amiodarone).

22. The uses of monitoring are
to assess adherence to therapy
to individualize therapy
to diagnose toxicity
to guide withdrawal of therapy
to determine whether a patient is already taking a drug before starting therapy (eg theophylline in an unconscious patient with asthma)
in research (eg to monitor for drug interactions in post-marketing surveillance using population pharmacokinetics).

23. Altered pharmacokinetic profile
liver metabolism
Disease
Pharmacogenetics (cytochrome P450 polymorphisms)
renal impairment
Elderly