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Agents and Actions

, Volume 39, Issue 3–4, pp 157–165 | Cite as

Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam

  • Thomas J. Carty
  • Anthony Marfat
  • Peter F. Moore
  • Fred C. Falkner
  • Thomas M. Twomey
  • Albert Weissman
Inflammation

Abstract

Ampiroxicam is a nonacidic ether carbonate prodrug of piroxicam. Our results demonstrate that, in contrast to piroxicam, ampiroxicam does not possess detectable prostaglandin synthesis inhibitory activityin vitro. Ampiroxicam, however, has similarin vivo potency to piroxicam in suppressing paw swelling in rat adjuvant arthritis. In an acute model of paw inflammation in rats, ampiroxicam is less potent than piroxicam itself: the ED50's of ampiroxicam are 9- and 3.5-fold higher than those of piroxicam following a single or multiple (5) daily oral doses, respectively. Using the phenylbenzoquinone stretching test as a method of evaluating acute analgetic activity, the ED50 for ampiroxicam is about 3-fold higher than that of piroxicam. These tests of activity share the property of being partially prostaglandin-dependent. Ampiroxicam itself is not observed in plasma after oral dosing to man [24], nor in the rat, dog, and monkey as reported here. Bioavailability studies show that conversion to piroxicam is about 100%, 90%, 70%, and 50% in these four species, respectively. These results indicate that ampiroxicam's anti-inflammatory activity is producedin vivo by conversion to piroxicam and support its credentials as an efficacious prodrug of piroxicam.

Keywords

Ether Arthritis Prostaglandin Oral Dose Piroxicam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations Used

AA

arachidonic acid

ACN

acetonitrile

AUC

area under the curve

Cmax

maximal achievable plasma concentration of drug

CO

cyclooxygenase

DiHETEs

dihydroxyeicosatetraenoic acids

DMSO

dimethylsulfoxide

ED50

dose causing 50% inhibition

5-HETE

5-hydroxyeicosatetraenoic acid

HOAc

acetic acid

HPLC

high performance liquid chromatography

IC50

concentration causing 50% inhibition

LTB4

leukotriene B4

MPE50

dose which causes 50% of the maximal protective effect achieved with a standard agent

NSAID

non-steroidal anti-inflammatory drug

PBQ

phenylbenzoquinone

PGD2

prostaglandin D2

RBL-1

rat basophilic leukemia cell line

RFE

rat foot edema

Tmax

time required to reach maximum drug concentration in plasma

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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • Thomas J. Carty
    • 1
  • Anthony Marfat
    • 4
  • Peter F. Moore
    • 1
  • Fred C. Falkner
    • 2
  • Thomas M. Twomey
    • 2
  • Albert Weissman
    • 3
  1. 1.Department of Immunology and Infectious DiseaseCentral Research, Pfizer IncGrotonU.S.A.
  2. 2.Department of Drug MetabolismCentral Research, Pfizer IncGrotonU.S.A.
  3. 3.Department of General PharmacologyCentral Research, Pfizer IncGrotonU.S.A.
  4. 4.Department of Medicinal ChemistryCentral Research, Pfizer IncGrotonU.S.A.

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