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

  • Inflammation
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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.

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Abbreviations

AA:

arachidonic acid

ACN:

acetonitrile

AUC:

area under the curve

C max :

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

T max :

time required to reach maximum drug concentration in plasma

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Authors and Affiliations

  1. Department of Immunology and Infectious Disease, Central Research, Pfizer Inc, 06340, Groton, CT, U.S.A.

    Thomas J. Carty & Peter F. Moore

  2. Department of Drug Metabolism, Central Research, Pfizer Inc, 06340, Groton, CT, U.S.A.

    Fred C. Falkner & Thomas M. Twomey

  3. Department of General Pharmacology, Central Research, Pfizer Inc, 06340, Groton, CT, U.S.A.

    Albert Weissman

  4. Department of Medicinal Chemistry, Central Research, Pfizer Inc, 06340, Groton, CT, U.S.A.

    Anthony Marfat

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Carty, T.J., Marfat, A., Moore, P.F. et al. Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam. Agents and Actions 39, 157–165 (1993). https://doi.org/10.1007/BF01998969

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