To:  Janet Simpson  and  Mary Neibert
Re:  Paxil

        Of the serotonin reuptake inhibitors,  paroxetine(Paxil) and
sertraline(Zoloft) have the shortest half-lives.  However,  nothing has yet
been published on paroxetine transmission into human milk.  In addition,  it
is known to reduce the seizure threshold in some patients.  This would not
be ideal for an infant.   One published report(J.Clin.Psy 56(6):243, 1995)
on sertraline suggests minimal levels in breastmilk and undetectible levels
in the infant.  If (and this is a big IF) a mother chooses to breastfeed
while using SSRIs,  then  lets try to use one we know a little
about(Sertraline).   Other published data suggest that Prozac may not be
preferred due to significant accumulation in at least one infant.

        I would still be very hesitant to use this family of drugs in a
breastfeeding mom,  but I'm sure you are all getting tird of hearing this !!!!!


---------------------------------------------

To: Jill Meltzer
Re:  Medications and timing of breastfeeding

        Your perception of drug re-uptake into the maternal circulation was
correct.

          The most important process that controls entry of drugs into human
milk is the plasma level,  followed closely by protein binding,  and lastly
the molecular weight of the drug.   Regardless of drug,  as the plasma level
rises and reaches a peak, the peak rate of entry into human milk occurs.
In addition,  as the plasma level drops,  the rate of entry into human milk
drops similarly.  Then as the levels in the maternal plasma compartment
drops,  equilibrium forces push drugs from the  milk back into the mothers
plasma compartment.  We must remember that milk is just another compartment
in the body,  just like other compartments (Liver, heart, brain, fat
tissues).   Drugs flow into the milk compartment,  and they flow out of the
compartment(this has been repeatedly documented in the literature).   The
principles that vary,   are the rate coefficients of entry, and exit...
these may vary depending on the drugs' physicochemical properties(pKa, lipid
solubility, protein binding, etc).

        Some drugs become sequestered into human milk,  and their exit rate
is reduced.  This is typical of lithium and iodides,  but few others.
These drugs undergo physical changes that prevent their re-entry into the
blood stream.   Other drugs become soluble in the triglyceride droplets in
milk.  Although this does not stop their re-entry into the mothers plasma,
it may slow its re-entry.

        Literally hundreds of articles reporting breastmilk levels of
selected drugs indicate that the levels tend to rise with the maternal peak,
and subsequently fall as the maternal peak drops off.   Although there is
significant milk stored in the alveolar lumen(breast) in between feedings,
much of the milk,  particularly the triglyceride components,  are created
and secreted during the feeding process.   As this occurs,  the capillary
supply swells,  increasing blood blow to the area,  and increasing the rate
of  breast milk production.  This is probably why we see dramatic swings in
the concentration of drugs in breastmilk as a function of maternal plasma
level.  This is also why it is important to attempt to choose breastfeeding
intervals,  when the maternal plasma level of a selected drug is LEAST.  At
this point,  we have the least transmission of drug to the milk,  and the
infant.

        In addition,   many drugs are tightly bound to albumin while being
transported in the plasma compartment,  while the unbound (free or soluble)
drug is free to transport into the lumen of the alveolus(milk).  At peak
levels  in the plasma,  the amount of free drug is maximum.   As the
maternal plasma level drops,  the binding efficiency of the drug to albumin
increases,  leaving less free(soluble) drug to transfer to the milk.  Again,
another reason we want to stay away from peaks.

        Breastfeeding around the peak levels works wonderfully for shorter
half-life drugs,  it works less well for drugs with long half-lives,  but if
you can wait long enough,  it will even work with these drugs.  Even though
many of the antidepressants have long half-lives,  if you wait 12 hours or
more before breastfeeding,  their peaks are significantly reduced,  thus
reducing exposure the infant to higher milk levels.    This process may not
always work,   but with most drugs,  its very effective at reducing overall
exposure.   If you have any further questions,  please email me direct or call.





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T.W. Hale, Ph.D.
Associate Professor of Pediatrics
Texas Tech University School of Medicine

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