Withdrawal Index
5. General Comment On Drug Half-Life
If the frequency of taking a capsule/tablet (say 12 hours) is much
shorter than the drug half life (say 24 hours), the capsule/tablet
may be eliminated at something like three times the period of the
half-life to reduce the average drug level slowly. The residual drug
from the other capsules/tablets sustains the background level. If
the frequency of elimination of a capsule/tablet is more than five
times the half life, it will fall temporarily but then build back
to its previous level.
For short half-life drugs taken twice or three times per day the drug
reduction needs to be achieved in fractions of tablets with a consolidation
period in between. The concentration in the body does not float down
but reduces more rapidly according to the intake. Therefore the reduction
here will need to be in small increments as the body levels fall so
quickly. The greater the dependency the longer the consolidation will
be needed between step changes in dosage and the smaller the size
of the reduction acceptable.
A given drug will have an inherent half-life range in
the body. To achieve a longer half-life various techniques may be
adopted. It is possible to have coatings on capsules/particles within
capsules where the inner ones dissolve later and therefore release
their drug more slowly.
Some drug particles are coated to slow down dissolution in the body.
Double and triple coatings will give slower dissolution rates. However
this technique can only be applied for as long as it takes the drug
to pass through the body. If a longer half-life is required, a chemical
intermediary can be used. Here the entire dose will be released into
the blood stream but part of it will be in the form of a related drug
which breaks down into the required drug over a period of several
days. This can allow longer half lives to be achieved.
Antidepressant Half Life Information
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Sep-01 |
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| drug |
generic name |
company |
type |
max mg/day |
Half life, hrs |
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| Anafranil |
clomipramine |
Novartis |
TCAD |
250 |
21(19-37) |
|
| Asendis |
amoxapine |
Wyeth |
TCAD |
300 |
no info |
|
| Cipramil |
|
Lundbeck |
SSRI |
60 |
36 (28 - 42) |
|
|
Elderly patients may metabolise more slowly and need
lower dose |
|
| Edronax |
|
Pharmacia |
SNRI |
12 |
8 |
|
| Efexor |
venlafaxine |
Wyeth |
SSNRI |
375 |
5 (5 to 11) |
|
| " XL |
|
Wyeth |
SSNRI |
225 |
20 to 22 |
|
| Faverin |
|
Solvay |
SSRI |
300 |
21 |
|
| Lentizol |
amitriptyline hyd. |
Pfizer |
|
200 |
15 (10 - 28) |
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Nortriptyline,
the most important metabolite, has a half-life of 36 hours (18-60 hours).
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It
has a polymorphically controlled metabolism (debrisoquine metabolism). In
subjects |
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with a slow metabolism (in Switzerland about 9% of
the population) high therapeutic |
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doses can lead to toxic plasma levels very quickly. |
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| Lustral, |
sertraline |
Pfizer |
SSRI |
200 |
26 (22 to 33) |
|
| Prothiaden |
dothiepin hyd. |
Knoll |
TCAD |
150 |
19 to 33 |
|
| Prozac |
fluoxetine |
Dista |
SSRI |
|
7 to 9 DAYS |
|
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Approx. 7% of people have difficulty metabolising
fluoxetine and it then increases rapidly |
| Seroxat |
paroxetine |
GSK |
SSRI |
50 |
21 to 26 |
|
| Sinequan |
doxepin |
Pfizer |
TCAD |
100x3 p.d. |
28 to 52 |
|
| Surmontil |
trimipramine |
Futuna |
TCAD |
300 |
24 |
|
| Tofranil |
imipramine |
Novartis |
TCAD |
200 |
19 |
|
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Elderly shown to have slower metabolism giving half
life of 28 hours. |
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Young me shown to have higher metabolism giving half
life of 16 hours. |
|
| Triptafen |
phenothiazine |
Goldshield |
TCAD |
4 tabs daily |
30 |
|
| Zispin |
mirtazapine |
Organon |
N&S enhancer |
45 |
20 to 40 |
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