RE: [NMusers] Multiple amniotic fluid samples

Dear Dr. Hutson,
The general methodological approach with amniotic fluid PK modeling is =
to pool the fluid from all the sacs at a given time point and measure =
the concentration in that pooled fluid. The concentrations in the =
amniotic fluid are generally modeled as a single compartment with other =
compartments representing the fetus, the placenta, and maternal plasma. =
There is some elegant work from Dr. Boudinot's group in this area (see =
below). If you have measured amniotic concentrations from different sacs =
at each time point then that variability can be simply assigned to noise =
(sigma) as indicated by Dr. Gibiansky.
 
For my Ph.D. work we were interested mainly in fetal PD and =
maternal/fetal PK are summarized in the JPET paper indicated below. =
Fetal PK can be easily modeled by simultaneously analyzing maternal =
plasma, fetal plasma, and overall fetal tissue concentrations (Both =
fetal amount and fetal plasma concentrations are needed to estimate the =
fetal volume of distribution)
 
Huang CS-H, Boudinot FD and Feldman S. Maternal-fetal pharmacokinetics =
of zidovudine in rats. Journal of Pharmaceutical Science 1996; 85: =
965-970.
Samtani MN, Pyszczynski NA, Dubois DC, Almon RR, Jusko WJ. Modeling =
glucocorticoid-mediated fetal lung maturation: I. Temporal patterns of =
corticosteroids in rat pregnancy. JPET. 2006 ;317:117-26.
 
Warm regards...MNS


-----Original Message-----
From: owner-nmusers_at_globomaxnm.com =
[mailto:owner-nmusers_at_globomaxnm.com]On Behalf Of Paul Hutson
Sent: Tuesday, January 15, 2008 1:54 PM
To: NMUSERS_at_GLOBOMAXNM.COM
Subject: [NMusers] Multiple amniotic fluid samples


Has anyone suggestions on how best to code for data that presents =
maternal plasma and multiple amniotic fluid concentrations? In addition =
to multiple other data points of plasma from various doses and routes =
for this tox study, I have simultaneous concentration data from 3 =
mouse dams (plasma) and samples from the amniotic fluid of three of each =
of their embryos.

Modeling each embryo as another compartment, especially with only the =
one concentration, is cumbersome and obviously doesn't converge.
Should the different embryonic AF concentrations be modeled as =
'repeated' samples at this same time point of a specific (AF) =
compartment, and the differences between them modeling as =
interoccassion or as an intrasubject variability (ERR)? The latter =
approach is the one I have taken, but I seek other suggestions as well.
Thank you in advance!


--


Paul R. Hutson, Pharm.D.

Associate Professor

UW School of Pharmacy

777 Highland Avenue

Madison WI 53705-2222

Tel 608.263.2496

Fax 608.265.5421

Pager 608.265.7000, p7856


Received on Tue Jan 15 2008 - 16:15:32 EST