Biology Reference
In-Depth Information
clearance is apparently zero; that is, the rate of chemical input equals the rate of chemi-
cal output and thus V ss is a volume term that is independent of clearance:
D
[
AUMC
AUC
]
V
ss =
(4)
.
2
[
]
The determination of AUC and AUMC is discussed in more detail under
Noncompartmental Models, statistical moment theory and noncompartmental analysis.
With all things being equal regarding the total amount of chemical in the body, the
plasma concentration at pseudo-equilibrium conditions will always be lower than that
during steady state, therefore V area tends to be higher than V ss . The reader should be
aware that V c values have limited application - although they can help predict initial
maximum plasma concentration after an iv bolus, and adverse health effects can be
correlated with this concentration. V area can be used to estimate the residual amount of
a chemical during the elimination phase, and V ss is more relevant as in clinical phar-
macology for accurately predicting the loading needed to achieve an instantaneous
desired plasma concentration before steady-state infusion.
Blood-Brain Barrier
The blood-brain barrier, which protects the central nervous system, is not an absolute
barrier. 2,4-Dichlorophenoxyacetic acid (2,4-D), for example, has been measured in
the rabbit brain after an iv dose ( Kim et al., 1996 ). The tight junctions of the capil-
lary endothelial cells and the surrounding glial cell processes are the main structural
features that contribute to the low permeability of the blood-brain barrier. Chemicals
that circulate in the blood must pass through the capillary endothelial cell membrane
and the glial cell membrane to enter the interstitial fluid of the brain. The low protein
content of the brain's interstitial fluid limits lipophilic chemicals that are tightly bound
to plasma proteins. Chemical access to the brain, then, is limited to those species that
are free (unbound), lipophilic, nonionized, and transported by specialized carrier sys-
tems, whereas ionized and highly plasma protein bound chemicals are excluded by the
blood-brain barrier. Another barrier to brain access is the presence of an adenosine
5 -triphosphate-dependent multidrug-resistance protein, which transports intracellular
chemicals back into the extracellular space. Since the blood-brain barrier is not fully
developed at birth, the risk of toxicity from exposure to some chemicals is higher for
newborns and young children than it is for adults.
Placental Transfer
Functions of the placenta include delivery of nutrients to the fetus, removal of fetal
waste, and maternal/fetal blood gas exchange, which suggests that many chemicals
move freely across the placental membrane. In the framework of distribution, the
placenta is not a barrier to protect the fetus from exposure to toxicants. Rather, the
Search WWH ::




Custom Search