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Re: [NMusers] Using sparse data to develop Population PK model for pediatrics

From: DAPING ZHANG <daping.debbie.zhang_at_gmail.com>
Date: Tue, 9 Jun 2015 00:04:19 -0500

Dear Jacob,

Thanks a lot for your comments. I am also very appreciated the reference
you sent to me.

Regarding to your questions, the purpose of this study was to explain the
PK variability of an immunosuppresant drug in pediatric population post
hematopoietic stem cell transplantation. The age ranges from 8 months to 12
years old.

The CL and V are comparable to literature adult values if the effect of
body size was accounted for a priori by allometric scaling of CL and V
in the construction of base model. But the RSE of the intra-individual
variability is large.

To test my assumptions, what models do you suggest to use?

Regards,
Daping


On Mon, Jun 8, 2015 at 3:25 AM, Jacob Brogren <jacob.brogren_at_qpharmetra.com>
wrote:

> Dear Daping,
>
>
>
> In order to provide more than just general comments it would be useful to
> get some more information.
>
>
>
> - What is the purpose of developing the PopPK model?
>
> - What is the medical condition/disease?
>
> - What is the relation between plasma concentration and clinical
> effect/safety?
>
> - What age groups are included in your data set?
>
>
>
> You have a limited number of patients in your data set, which is often the
> case with pediatric studies. There are different opinions about this, but I
> think you are doing the right thing to compare your estimates with
> literature values as a sanity check. Maybe you should consider including
> previous data or use parameters found in the literature as priors.
>
>
>
> As you probably know, the dependence of PK parameters on body size and
> organ maturation is frequently incorporated in pediatric PopPK models. You
> can find more information in the scientific literature (Anderson and
> Holford, 2013) about how to implement this.
>
>
>
> You assumed that all concentrations in one individual was resulting from
> the same dose. Further, you assumed no drug accumulation (three times daily
> dosing seem to be in line with that). These assumptions can in theory be
> tested by using alternative models and comparing how well the different
> models fit your data. But again, your data is limited and some models may
> not run.
>
>
>
> Please feel free to tell us more about your problem.
>
>
>
> Best Regards
>
>
>
> Jacob Brogren
>
>
>
> Ref.
>
> Anderson, Brian J., and Nick HG Holford. "Understanding dosing: children
> are small adults, neonates are immature children." Archives of disease in
> childhood 98.9 (2013): 737-744.
>
>
>
>
>
> *Jacob Brogren, MSc*
>
> Senior Consultant
>
> [image: Description: QPharmetra_noTag_FA little.png]
>
> +46 72-350 88 69 (M)
>
> jacob.brogren_at_qpharmetra.com | http://qPharmetra.com
> <http://qpharmetra.com/>
>
>
>
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>
> *From:* owner-nmusers_at_globomaxnm.com [mailto:owner-nmusers_at_globomaxnm.com]
> *On Behalf Of *DAPING ZHANG
> *Sent:* den 3 juni 2015 03:29
> *To:* nmusers_at_globomaxnm.com
> *Subject:* [NMusers] Using sparse data to develop Population PK model for
> pediatrics
>
>
>
> Dear all,
>
>
>
> I would like to develop a population PK model for a drug used in
> pediatrics. We got drug concentrations from 15 patients. The drug was given
> 3 times a day. Only one plasma sample were drawn every week for 4 weeks.
> They record the exact sampling time after drug was given. So for each
> patient, we had 4 concentrations from 4 weeks.
>
>
>
> I assumed all the 4 samples were from one dose and developed a Pop PK
> model. This assumption did not consider disease progress and drug
> accumulation. The result was still comparable with literature. I will be
> very appreciated your comments and suggestions for this model.
>
>
>
> Regards
>
>
>
> --
>
> Daping Zhang
>
> Ph.D. Candidate
>
> University of Houston
>
>
>



--
Daping Zhang
Ph.D. Candidate
Department of Pharmacological & Pharmaceutical Sciences (PPS)
University of Houston
Cell: 713-855-9668
E-mail Address: dzhang11_at_uh.edu

Received on Tue Jun 09 2015 - 01:04:19 EDT

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