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>> Randy scribbled:"One of the recent discussants in the Annals
>>suggested disruption of enterohepatic recirculation of phenytoin
>>as a possible mechanism."
>
> If this was the case, then which bug in our guts does cipro kill that the
> other broad spectrum antibiotics don't?? If enterohepatic recycling was one
> possible reason, then would we not expect to see a heck of a lot more people
> with weird phenytoin levels given the vast amount of broad spectrum
> antibiotics that are currently being used?
Agreed. Why would ciprofloxacin (and perhaps other
fluoroquinolones) have this effect if other antibiotics
effective against gut flora don't. One of the discussants in
the Annals also raised the point that both phenytoin and
ciprofloxacin have been around for awhile--why are case
reports about this so recent?
>> BTW, "Patient was rebolused (maintenance therapy the same) and two
>>days later the phenytoin concentration was 77 mcmol/L."
> Rebolused with........(?) mg, if this was a significant amount, and with t1/2
> approx 20 hours, saturable metabolism/nonlinear PK, 77micromol/L may not be
> surprising, be nice to see another when he/she is a little more stable at
> steady state a little further down the road. :-)
Bolus was 600 mg. Phenytoin concentration five days after was 98.
So, (1) initial bolus of 750mg & maintenance of 100 mg tid--
two days later, concentration was 37
(2) cipro was stopped--additional bolus of 600 mg given--
maintenance continued
(3) two days later concentration was 77
(4) three days after that (5 after 2nd bolus) concentration
was 98.
We still think cipro was having an effect when it was on
board. No other data available. Patient expired.
>Question - if biliary excretion is significant for phenytoin
>elimination: how much phenytoin/metabolites is present in bile?
>What % of CLtb is CLbil? In other words, is it relavent? Does cipro
>alter/inhibit phenytoin's biliary excretion? Effect of disease
>states...??
If AUC is smaller and half-life is shorter when cipro is given
concurrently, then if it does affect biliary excretion it would have
to enhance it; and if it affects reabsorption from the gut it would
have to inhibit it. I don't think this has been studied. Can't say
what effect disease states would have.
***************************************
Randy Trinkle, BScPharm, BA
Clinical Pharmacist
Cross Cancer Institute
Edmonton, AB
mailto:rtrinkle.-a-.datanet.ab.ca
Health Science links:
http://www.datanet.ab.ca/users/rtrinkle
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)