Page 397 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

364 SECTION | IV Drugs of Use and Abuse

VetBooks.ir TABLE 21.2 Some NSAID Drug Interactions ibuprofen died from respiratory failure and asystole
approximately 12 h postexposure (Cathers et al., 2000).
Ketoprofen given as a subcutaneous dose of 2 mg/kg to 3-
Drugs that Decrease Absorption of Some NSAIDs
month-old kittens and mature cats produced lesions in the
Aluminum hydroxide
small intestine that were more severe in adult cats (Takata
Drugs that Compete for Protein Binding with NSAIDs et al., 2012).
Acetazolamide Naproxen induced toxicosis in dogs at a dose of
5 mg/kg/day, and plasma concentrations were .50 μg/mL
Corticosteroids
(Daehler, 1986; Rubin and Papich, 1990; Boothe, 2001).
Coumarin Severe toxicosis was produced in a Samoyed dosed with
Digitoxin 5.6 mg/kg naproxen, presumably once per day, over a
week. Common clinical signs are anemia, melena, and
Hydantoin
renal and hepatic dysfunction. A perforating ulcer was
Methotrexate
described in a dog given 10 20 mg/kg/day naproxen for
Phenylbutazone several weeks (Daehler, 1986). Doses of 15 mg/kg/day
have been lethal in some dogs (Daehler, 1986; Gfeller
Phenytoin
and Sandon, 1991). Horses do not appear to be sensitive
Salicylates
to naproxen toxicosis. Horses given three times the
Sulfonamides recommended dose of naproxen for 6 weeks did not have
Tolbutamide adverse clinical signs (Boothe, 2001).
Phenylbutazone is commonly used in horses. The
Valproic acid
recommended oral dose is 4 mg/kg/day (Plumb, 2015). A
Drugs that Increase Metabolism Rate of Some NSAIDs
dose of 4.4 mg/kg every 12 h over a 2-week period was
Antihistamines associated with changes of mineralization patterns in cor-
tical bone in growing horses 18 30 months of age, an
Phenobarbital
effect that was reversible (Brumbaugh, 2001). The same
Phenytoin
dose has been associated with other clinical signs, includ-
Rifampicin ing CNS depression and protein-losing enteropathy.
Drugs that Decrease Metabolism Rate of Some NSAIDs Shock was reported in one of nine horses after 5 days of
dosing (Collins and Tyler, 1985). Therapeutic plasma
Anabolic steroids
concentrations for phenylbutazone in a horse range from
Chloramphenicol 10 to 30 μg/mL. The therapeutic range in humans,
Drugs that Increase Excretion Rate of Some NSAIDs 100 150 μg/mL, would be lethal in a horse (Lees et al.,
1991). Phenylbutazone doses of 100 mg/kg/day did not
Aluminum hydroxide
cause gastrointestinal ulcers in dogs (Mazue ´ et al., 1982).
Magnesium hydroxide
Vultures are exquisitely sensitive to some NSAIDS,
Drugs that Decrease Excretion Rate of Some NSAIDs which has led to their near extinction in parts of Asia after
Probenecid diclofenac entered their food chain. Diclofenac and keto-
profen are known to cause renal failure in Old World
Methotrexate
vultures, and carprofen, flunixin, and phenylbutazone pro-
An incomplete list of NSAID-drug interactions. For more detailed duced clinical toxicosis in experimental vultures (Fourie
information, consult Verbeeck (1990).
et al., 2015).
Doses of 175 250 mg/kg have been associated with acute
renal failure. Serum ibuprofen concentrations less than Toxicokinetics
31 μg/mL have not been associated with clinical signs in NSAIDs are small, weakly acidic molecules with pK a
dogs, but melena was noted with serum concentrations of values less than 4.5, and thus, are well-absorbed in the
138 μg/mL. stomach (Mazue ´ et al., 1982; Kore, 1990; Rubin and
Less information on ibuprofen in cats is available, Papich, 1990; Verbeeck, 1990; Isaacs, 1996; Boothe,
though they are considered very susceptible. Cats dosed 2001). Peak plasma concentrations for most NSAIDs
with 50 mg/kg ibuprofen had gastrointestinal hemorrhage occur within 3 h of oral dosing. Some absorption probably
and irritation (Kore, 1990). Doses of 200 mg/kg were occurs in the proximal small intestine.
associated with renal failure, and doses over 600 mg/kg Ibuprofen and naproxen are 60% 80% and
caused death. A ferret that ingested at least 347 mg/kg 68% 100% bioavailable, respectively, in dogs (McKellar