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Does anyone have information regarding tissue concentrations and half-life
of metronidazole when used to treat clostridium difficle colitis? We have
come across an order for 500mg bid. We are now retrospectively trying to
evaluate if the dosing interval was appropriate based on tissue t 1/2 or if
the dose was high enough where the dosing interval would not really matter.
Thanks,
Michelle L. Champion, R.Ph., PharmD
Clinical Pharmacist, UPMC South Side
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The half-life of metronidazole is about 6-12 hours. Metronidazole is
well absorbed after oral administration. The pharmacologic effect in C.
difficile colitis probably results from secretion of the drug from the
blood back into the intestine after initial systemic absorption.
Although one could argue that 500 mg BID is likely to be as effective as
250 mg Q 6 h, I am not aware of any clinical studies using 500 mg BID.
David Nix, Pharm.D.
The University of Arizona
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Although there are no clinical trials to prove it, it is reasonable to
expect, on theorical grounds, that higher doses of metronidazole would be
more effective than smaller doses given more frequently. Like
fluoroquinolones and aminoglycosides, metronidazole shows
concentration-dependent dynamics, at least in vitro.
The sometimes necessary use of iv metronidazole for C dif is not
convincingly explained by the secretion of the drug into the lumen of the GI
alone. What may be an equally important possibility is that iv metronidazole
is better able to reach persistent pockets of C dif in places like the bile
tree.
However, I have not been able to find anything in the literature on this
point.
Nasr H. Anaizi, PhD RPh
Clinical Pharmacy Specialist
Associate Prpf. of Pharmacology & Physiology
University of Rochester Medical Center
601 Elmwood Ave, Box 638
Rochester, NY 14642
Phone: (716) 275-1696
Fax: (716) 756-5582
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My intuitive response is that bid dosing would not be
effective - rationale is diarrhea = decrease in
GI transit time = decreased exposure of organism to
antibiotic.
Then I looked for evidence yea or nay. I found one
trial of metronidazole bid which failed to clear asymptomatic
fecal carriers:
Treatment of asymptomatic Clostridium difficile carriers (fecal
excretors) with vancomycin or metronidazole. A randomized,
placebo-controlled trial. Johnson S, Homann SR, Bettin KM, Quick JN,
Clabots CR, Peterson LR, Gerding DN Minneapolis Veterans Affairs
Medical Center, Minnesota.
Also interesting: when searching MEDLINE for
metronidazole AND "clostridium difficile"
and limiting search to randomized controlled trials there were only
14 hits. None of them used bid dosing.
Twice daily metronidazole might work but it's an untested
hypothesis.
***************************************
Randy Trinkle, BScPharm, BA
Pharmacy Department
Prince Rupert Regional Hospital
mailto:rtrinkle.-at-.mail.citytel.net
Health Science links:
http://www.rupert.net/~rtrinkle
***************************************
'What's the most important thing in life to you?'
Data.
'No, no--I mean, what makes you happy, satisfied?'
Good data.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)