Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 13 NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AND CHONDROPROTECTIVE AGENTS
mately 20 h in cats. Carprofen is eliminated in dogs
primarily by means of biotransformation in the liver,
followed by rapid excretion of the resulting metabolites
in feces (70–80%) and urine (10–20%). Some enterohepatic
circulation has been detected.
Adverse effects
● The majority of adverse events reported are those
typical for the NSAID class.
● Idiosyncratic hepatotoxicity has been reported in
dogs treated with carprofen. Labrador retrievers may
be overrepresented. The mechanism of the hepatotoxicity
is not known but it has been speculated that
glucuronide metabolites may react with plasma and
hepatocellular proteins, resulting in the formation of
antigenic NSAID-altered proteins that cause immunemediated
hepatic toxicosis. Drug withdrawal is
usually associated with recovery, but some cases
have been fatal.
● The safety of chronic carprofen use in cats has not
been determined. Duodenal perforation has been
reported in a cat treated with carprofen at a dose of
2.2 mg/kg q.12 h for 7 d. The considerably longer
half-life in cats compared to dogs indicates that
chronic dosage recommendations for dogs cannot be
extrapolated to cats.
Deracoxib
(Deramaxx ® )
Deracoxib is available in the United States, Europe
and Australia. Structurally it is closely related to celecoxib,
a coxib for humans. However, deracoxib is indicated
only for use in dogs.
Clinical applications
Deracoxib is indicated for management of pain and
inflammation associated with osteoarthritis and for
postoperative pain following orthopedic surgery. Additional
reports indicate it has been used in the treatment
of osteosarcoma.
Formulations and dose rates
Deracoxib is available as an oral chewable tablet.
DOGS
Orthopedic surgery
• 3–4 mg/kg PO q.24 h as needed for 7 d
Osteoarthritis
• 1–2 mg/kg PO q.24 h
Mechanism of action – additional information
Deracoxib is a member of the coxib class of NSAIDs.
Data indicate that it inhibits the production of PGE 1 and
6-keto PGF 1 by its inhibitory effects on prostaglandin
biosynthesis. Deracoxib inhibited COX-2 mediated
PGE 2 production in LPS-stimulated human and dog
whole blood. At doses of 2–4 mg/kg/d, deracoxib does
not inhibit COX-1 based on in vitro studies using cloned
canine cyclo-oxygenase.
Relevant pharmacokinetic data
Deracoxib has a half-life of approximately 3 h, although
a longer duration of effectiveness is observed. Nonlinear
elimination kinetics are exhibited at doses above 8 mg/
kg/d, at which competitive inhibition of constitutive
COX-1 may occur. At doses of 20 mg/kg, the half-life
increases to 19 h.
Adverse effects
Adverse events reported are those typical for the NSAID
class.
Dipyrone
(Generic)
Clinical applications
Dipyrone is approved for use in dogs and cats in Europe
and Canada, although its use in cats is strongly discouraged
as safety trials in this species are lacking. Even in
dogs, with the availability of newer, safer NSAIDs, there
is little reason to consider the use of dipyrone today. It
is a member of the pyrazolone class of NSAIDs. It has
been primarily used as an antipyretic agent, as the analgesia
produced is inadequate for moderate-to-severe
postoperative pain. However, it can control mild-tomoderate
visceral pain. The role of dipyrone in veterinary
medicine is very limited, particularly with the
development of newer, more effective and safer NSAIDs.
Its use in food-producing species is prohibited because
of its potential for causing blood dyscrasias in
humans.
The most common formulation in which dipyrone is
used clinically is in combination with hyoscine (e.g.
Buscopan®, Spasmogesic®) for the management of
abdominal pain in dogs and horses.
Formulations and dose rates
DOGS AND CATS
Dipyrone is available as a solution for injection and tablets.
• The dose is approximately 25 mg/kg PO or IV q.12 h or q8 h
• The injectable solution should preferably be used IV as IM or SC
injection causes tissue irritation
Relevant pharmacokinetic data
Dipyrone is rapidly and well absorbed following oral
administration in the dog, with an elimination half-life
of 5–6 h. It is largely excreted in the urine.
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