Dear all:
I am trying to figure out if there is any effect of enzyme genotype on the PK
of a drug and its active metabolites. But I don't know if I could use NONMEM to
do this with my data.
I have a dataset from multiple dose study. Drug was administered orally and
only one sample was taken from each patient at steady state. Parent drug and
three metabolites concentrations were measured. Each patient was genotyped.
Time since last dose was not recorded because the maximum concentration and
trough concentration varied only 3%.
Could NONMEM be used for this analysis? Any comment will be highly appreciated.
Best regards,
Huali
Missing time data
Huali,
This sounds like an ideal data set to determine if there are any effects of genotype on CL/F. You dont really need NONMEM - just look at the doserate/conc (i.e. CL/F) means for each genotype and do an ANOVA. Of course you can make it fancier and include other covariates such as weight, sex (a genotype), race etc. It can be done with NONMEM or almost any statistics package that supports multiple regression.
Nick
Huali Wu wrote:
> Dear all:
>
> I am trying to figure out if there is any effect of enzyme genotype on the PK of a drug and its active metabolites. But I don't know if I could use NONMEM to do this with my data. I have a dataset from multiple dose study. Drug was administered orally and only one sample was taken from each patient at steady state. Parent drug and three metabolites concentrations were measured. Each patient was genotyped. Time since last dose was not recorded because the maximum concentration and trough concentration varied only 3%. Could NONMEM be used for this analysis? Any comment will be highly appreciated. Best regards, Huali
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford
A number of emails seem to have been re-posted, which reminds me that I
had meant to comment on this.
With PREDPP, computation of steady state does not involve the value of
the TIME data item. You say that "time since last dose" was not
recorded. You can create a data set with pairs of events: the steady
state dose event record, followed by the observation event record. Use
the same value of TIME for both. The value of TIME on the records
(e.g., 0) will not have any effect. PREDPP will estimate the PK
parameters that affect the prediction such as CL, V, etc. depending on
which ADVAN you use.
On Tue, 4 Mar 2008 22:58:34 -0500, "Huali Wu"
<[EMAIL PROTECTED]> said:
> Dear all:
>
> I am trying to figure out if there is any effect of enzyme genotype on
> the PK of a drug and its active metabolites. But I don't know if I
> could use NONMEM to do this with my data.
>
> I have a dataset from multiple dose study. Drug was administered
> orally and only one sample was taken from each patient at steady
> state. Parent drug and three metabolites concentrations were
> measured. Each patient was genotyped. Time since last dose was not
> recorded because the maximum concentration and trough concentration
> varied only 3%.
>
> Could NONMEM be used for this analysis? Any comment will be highly
> appreciated.
>
> Best regards,
>
> Huali
>
>
>
--
Alison Boeckmann
[EMAIL PROTECTED]