PharmPK Discussion - Metabolic stability of NCE's

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On 22 Jun 2003 at 08:01:59, tausif Ahmed (mailtaus.aaa.yahoo.com) sent the message


Dear all
I am involved in doing in vitro metabolism studies with various drugs
and NCE's. My query is that when we start the in vitro studies with the
new NCE's, what is the optimal concentration of the NCE at which we
should study the metabolic stability. Generally the concn. used is 10然.
Can any body tell me what is the rationale for using this concentration
or any other concentration for metabolic stability of the NCE's.

Regards
Tausif Ahmed
SRF, Dept. of Pharmaceutical Medicine,
Ranbaxy Clinical Pharmacology Unit,
Majeedia Hospital 2nd floor, Hamdard University,
New Delhi-110062

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On 24 Jun 2003 at 21:03:52, "d.s samiulla" (dssamiulla.at.yahoo.com) sent the message


Dear Tausif,

It is better to use 5 uM for screening, as 10uM isalsook. If an
sample shows inhibitionmore than 40%, then one can proceed for IC 50
determination for the same. The rationale behind this is, as modern
system is used for analysis (LC/MS/MS) is sensitive and also
highthrough-put, as in general substrate concentartion should be less
than Km, as system used for metabolic stability (use of liver
microsomes) is not sample hungry.

Regards,
Samiulla

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On 24 Jun 2003 at 21:09:37, "d.s samiulla" (dssamiulla.-a-.yahoo.com) sent the message


Dear all,

Could you please tell me how to do metabolic testing ofNCE's using
rat/human serum/plasma (as it contains esterases and amide oxidase) and
please mention the use of reference compounds for the same for the
standardisation of assay.

Samiulla

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On 6 Jul 2003 at 07:58:18, tausif Ahmed (mailtaus.aaa.yahoo.com) sent the message


Dear Samiullah

Thanks for your reply, but my query is that what is the scientific
rationale for using 10然 or 5然 concentration for metabolic stability
of NCE's.
Regarding the reason that the the concn. should be less tan the km
value of the compound, If we have a seies of NCE's with in the same
therapeutic class, should we determine the km value for each compound.
I think this is not practically feasible, moreover if we are comparing
it with a standard compound, is there a need to determine the km value
of this std. compound also.

Regards
Tausif Ahmed
SRF, Dept. of Pharmaceutical Medicine,
Ranbaxy Clinical Pharmacology Unit
Majeedia Hospital 2nd floor, Hamdard University,
New Delhi-110062
India

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