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Dear All,
working as a physician in psychiatry, I would be grateful if somebody =20=
could give me information how to deal with the active metabolite(s) of =20=
a drug - and its/their medical effect .
For example if I have to start the same medication again after =20
poisoning (at what time could I start again the medication ?) =96 only =
=20
working with elimination Half-live of the original drug ? ( perhaps =20
knowing the latest level of medication ?)
Seeking for advice in some books =96 I have not yet found the =20
apposite answer.
Thanks in advance,
Schrenk=
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I met the same problem about a active compound which has anti-
inflammation activity.
The protype of this compound is effective in both in vitro and in vivo
experiments, however, it has a very short half life. And its
metabolites are also regarded being avtive and have longer half
life.So what should I do with this compound? No reference has given
out the exact structure of these metabolites.I will be appreciateful
for any comments and suggestions.
Thanks
Feng
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The following message was posted to: PharmPK
Schrenk:
This is an interesting question with no easy answer. There is a wide
variation in half-lives between different psychiatric medications. One
of the psychiatric medications known to have a particularly long half-
life is fluoxetine. It can take several weeks for it's metabolite
norfluoxetine to reach steady-state and correspondingly several
several weeks to wash out of the system. The real problem is that
there is wide individual variability in half-life. For example, in
younger subjects norfluoxetine has a half life ranging from 7 to 15
days but in females over 75 years of age, the average half-life was 20
days. Individuals with genetic variants of CYP2C19 and CYP2D6 will be
at high risk for delayed elimination.
But the final confounder is that pharmacodynamic effects including
toxicity are not necessarily related to drug levels (and recovery can
lag behind pharmacokinetics).
Certainly for drugs where levels can be easily determined, determining
drug level is a good starting point (bearing in mind that activity
metabolites may lag behind parent levels). For drugs where levels can
not be determined, consider the PK properties of the drug including
metabolites and any individual risk factors for altered PK or PD
effects then restart the medication at a low dose and titrate slowly.
Sincerely,
Carol Collins MD
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