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Dear All,
Fluoroquinolone antibiotics are known to inhibitors of Theophylline
metabolism. Plenty of literature is available to show this interaction
using liver microsomes.(in-vitro)
We are trying to see this interaction in - vivo in experimental
animals.
I am not able to locate any such in-vivo reference in animals. Can
anyone suggest me one such reference.
Thanks.M.Khan
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[A few replies - db]
From: "Shoaf, Susan"
To: "'PharmPK.-at-.boomer.org'"
Subject: RE: PharmPK Fluoroquinolone - Theophylline interaction
Date: Wed, 5 Apr 2000 08:46:47 -0400
The effect of ciprofloxacin on theophylline pharmacokinetics in
healthy subjects.
Batty KT, Davis TM, Ilett KF, Dusci LJ, Langton SR
Br J Clin Pharmacol 1995 Mar;39(3):305-11
Pharmacokinetic interactions between theophylline and other
medication (Part I).
Upton RA
Clin Pharmacokinet 1991 Jan;20(1):66-80
These references were linked on David Flockarts Cytochrome P450 web page.
http://www.dml.georgetown.edu/depts/pharmacology/davetab.html
Susan Shoaf
Susan E. Shoaf, Ph.D.
Clinical Pharmacokineticist
Otsuka America Pharmaceutical, Inc.
---
Date: Wed, 5 Apr 2000 10:57:47 -0400
From: Del Castillo Jerome
X-Sender: delcastj.-a-.esi25.ESI.UMontreal.CA
To: PharmPK.at.boomer.org
cc: mkhan.at.looksmart.com.au
Subject: Re: PharmPK Fluoroquinolone - Theophylline interaction
Dear Mubeen Khan:
The inhibition of theophylline metabolism by fluoroquinolones has been exami=
ned
in dogs (see below).
Hope this helps. Sincerely,
J=E9rome del Castillo, DMV MSc
Universit=E9 de Montr=E9al
Facult=E9 de pharmacie
Facult=E9 de m=E9decine v=E9t=E9rinaire.
___________
J Vet Pharmacol Ther 1995 Oct;18(5):352-6
Enrofloxacin-theophylline interaction: influence of enrofloxacin on=20
theophylline
steady-state pharmacokinetics in the beagle dog.
Intorre L, Mengozzi G, Maccheroni M, Bertini S, Soldani G
Laboratory of Veterinary Pharmacology and Toxicology, University of=20
Pisa, Italy.
Enrofloxacin, a quinolone antibiotic developed exclusively for use in animal=
s,
was investigated for its effects on the steady-state pharmacokinetics of
theophylline in six healthy Beagle dogs. A sustained-release theophylline
formulation was given alone (20 mg/kg per os twice daily at 12 h intervals) =
for
9 days and then co-administered with enrofloxacin (5 mg/kg i.v. once a day) =
for
5 days. Mean trough theophylline concentrations progressively and significan=
tly
increased during the five days of enrofloxacin co-administration. Theophylli=
ne
clearance and concentration-time profile were significantly changed by
enrofloxacin co-administration. No significant change was observed in
enrofloxacin pharmacokinetics. The kinetic interaction between theophylline =
and
enrofloxacin could be of clinical significance and may require plasma drug
concentration monitoring and adjustment of theophylline dosage.
MeSH Terms:
Administration, Oral
Animal
Anti-Infective Agents, Fluoroquinolone/pharmacology*
Anti-Infective Agents, Fluoroquinolone/blood
Anti-Infective Agents, Fluoroquinolone/administration & dosage
Bronchodilator Agents/pharmacokinetics*
Bronchodilator Agents/blood
Bronchodilator Agents/administration & dosage
Delayed-Action Preparations/pharmacokinetics
Delayed-Action Preparations/administration & dosage
Dogs/metabolism*
Drug Interactions
Injections, Intravenous/veterinary
Quinolones/pharmacology*
Quinolones/blood
Quinolones/administration & dosage
Support, Non-U.S. Gov't
Theophylline/pharmacokinetics*
Theophylline/blood
Theophylline/administration & dosage
Substances:
enrofloxacin
Theophylline
Quinolones
Delayed-Action Preparations
Bronchodilator Agents
Anti-Infective Agents, Fluoroquinolone
---
Date: Wed, 05 Apr 2000 10:48:17 -0700
From: "David Nix, Pharm D."
Organization: College of Pharmacy
To: PharmPK.at.boomer.org
Subject: Re: PharmPK Fluoroquinolone - Theophylline interaction
Most references in animals have been concerned with convulsent potential
of fluoroquinolones, but many included pharmacokinetic data.
Try the following references:
<1>
UI 98351348
AU Levasseur LM. Delon A. Greco WR. Faury P. Bouquet S. Couet W.
TI Development of a new quantitative approach for the isobolographic
assessment of the convulsant interaction between pefloxacin and
=20 theophylline in rats.
SO Pharmaceutical Research. 15(7):1069-76, 1998 Jul.
<4>
UI 95303792
AU Davis JD. Aarons L. Houston JB.
TI Effect of norfloxacin on theophylline disposition: a
=20 comparison with other fluoroquinolones.
SO Pharmaceutical Research. 12(2):257-62, 1995 Feb.
<5>
UI 93121992
AU Vancutsem PM. Schwark WS.
TI Effects of fluoroquinolone antimicrobials alone and in
=20 conjunction with theophylline on seizures in amygdaloid
=20 kindled rats. Mechanistic and pharmacokinetic study.
SO Epilepsy Research. 13(1):59-71, 1992 Oct.
<6>
UI 92148686
AU Hasegawa T. Nadai M. Apichartpichean R. Muraoka I. Nabeshima T.
Takagi K.
TI Pharmacokinetic characteristics of N7-substituted
=20 theophylline derivatives and their interaction with
=20 quinolone in rats.
SO Journal of Pharmaceutical Sciences. 80(10):962-5, 1991 Oct.
=20 Edwards DJ. Waite NM. Svensson CK. Effect of enoxacin and
4-oxo-enoxacin on antipyrine disposition in the rat.
Drug Metabolism & Disposition. 16(4):653-5, 1988
---
From: GLDrusano.at.aol.com
Date: Wed, 5 Apr 2000 14:21:14 EDT
Subject: Re: PharmPK Fluoroquinolone - Theophylline interaction
To: PharmPK.-at-.boomer.org
Why bother with animals. There are data in man. Search under enoxacin.
George
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Mubeen
During my PhD work at Manchester University, we looked at this theophylline
interaction in the rat, using enoxacin/ciprofloxacin/norfloxacin. We showed
a fluoroquinolone concentration dependent reduction in theophylline
clearance. Using steady state experiments, we showed that enoxacin was the
most potent in terms of its effect on theophylline clearance.
Have a look at the following:
Davis JD, Aarons L, Houston JB
Xenobiotica 1995 Jun;25(6):563-573
Metabolism of theophylline and its inhibition by fluoroquinolones in rat
hepatic microsomes.
Davis JD, Aarons L, Houston JB
Pharm Res 1995 Feb;12(2):257-262
Effect of norfloxacin on theophylline disposition: a comparison with other
fluoroquinolones.
Davis JD, Aarons L, Houston JB
Pharm Res 1994 Oct;11(10):1424-1428
Relationship between enoxacin and ciprofloxacin plasma concentrations and
theophylline disposition.
Davis JD, Brennan B, Aarons L & Houston JB
Br J Clin Pharmacol 1994; 38 (2): 178P
Effect of norfloxacin on theophylline disposition: A comparison with other
fluoroquinolones.
Davis JD, Aarons L, Houston JB
J Chromatogr 1993 Nov 17;621(1):105-109
Simultaneous assay of fluoroquinolones and theophylline in plasma by
high-performance liquid chromatography.
Davis JD, Brennan B, Aarons L & Houston JB
Br J Clin Pharmacol 1992; 34 (2): 169P
Steady state effects of ciprofloxacin and enoxacin on theophylline
pharmacokinetics.
Best wishes
John
(John_Davis.-at-.sandwich.pfizer.com)
PharmPK Discussion List Archive Index page
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