RE: 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
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] Behalf Of Paul Hutson
Sent: Tuesday, January 15, 2008 1:54 PM
To: [email protected]
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