The following message was posted to: PharmPKBack to the Top
Dear PharmPK members,
I am planning to perform a pharmacokinetic study of a compound in pregnant
mice, which will complement a teratogenic study of the same compound. The
drug will be injected to pregnant females at day 8.5 of gestation and at
various time intervals they will be sacrificed and the embryos collected
for analysis of drug/metabolite concentrations.
The major problem with this study is that the embryos are extremely small
(2-4 mm) and therefore there is very little tissue sample to work with. I
was thinking of taking the entire yolk sac for analysis since that at this
developmental stage there is no placenta and the barrier for drug diffusion
between maternal blood and the embryo is the yolk sac membrane. However, an
additional problem is that the embryonic drug concentration will need to be
normalized to the protein content in the embryonic homogenate.
My questions to the group members are:
Due to the difference (?) in concentration units, is a comparison between
maternal (e.g. mg/mL plasma) and embryonic (e.g. mg/mg protein) drug
concentration possible? How? Is there an alternative way of expressing
embryonic concentrations so that maternal/embryonic comparisons will be
feasible?
Has anyone in the group performed similar experiments and can share from
his experience?
Ofer Spiegelstein, Ph.D.
Center for Human Molecular Genetics
University of Nebraska Medical Center
Omaha, NE 68198-5455
Tel: 402-559-8187 (Office)
402-559-2863 (Lab)
402-559-4001 (Fax)
E-mail: ospiegel.at.unmc.edu
The following message was posted to: PharmPKBack to the Top
Regarding the expression of units it is more meaningful if it is expressed
as the ratio between maternal and embryonic concentrations. It can be
possible by calculating the total drug/metabolite concentrations in
maternal and embronic tissue. Ultimately in teratogenic studies the
relative drug concentrations are important and you can perform such studies
at different dose levels.
I suggest invitro diffusion studies using the embronic sac, which will give
estimate of drug permeability without the interference of protein which
will enable you to find out whether really drug diffuses through the sac.
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