The toxicity and biotransformation of single doses of acetaminophen in dogs and cats

Savides, Michael C.; Oehme, Frederick W.; Nash, S.; Leipold, H. W.

doi:10.1016/0041-008x(84)90266-7

Cited by 96 publications

(65 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cats are more susceptible to paracetamol toxicity than dogs because they are less efficient at metabolising paracetamol due to poor glucuronidation abilities, a much lower threshold for dose-dependent biotransformation and a capacitylimited sulphation pathway (Savides et al, 1984;Hjelle and Grauer, 1986;Aronson and Drobatz, 1996;Sellon, 2006).…”

Section: Paracetamol (Acetaminophen)mentioning

confidence: 99%

Poisoning of dogs and cats by drugs intended for human use

Cortinovis

Pizzo

Caloni

2015

The Veterinary Journal

View full text Add to dashboard Cite

Section: Paracetamol (Acetaminophen)mentioning

confidence: 99%

Poisoning of dogs and cats by drugs intended for human use

Cortinovis

Pizzo

Caloni

2015

The Veterinary Journal

View full text Add to dashboard Cite

“…For example, the metabolism of ketoprofen is dominated by glucuronidation reactions in dogs [25]. However, many studies have reported that glucuronidation in cats is limited [5,7,11,18,19,23,24,30]. Therefore, NSAIDs may induce more severely adverse-effects in cats compared with other species.…”

mentioning

confidence: 99%

Therapeutic and Adverse Effects of Flunixin-Meglumine in Adult and Young Cats

Takata

Hikasa

Satoh

2011

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (<3 months old) and adult (>12 months old) cats of both sexes were given LPS (0.3 g/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.KEY WORDS: flunixin-megulumine, gastrointestinal effect, lipopolysaccharide, nonsteroidal anti-inflammatory drug, pharmacokinetics.J. Vet. Med. Sci. 73(12): 1591-1596, 2011 Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used analgesics in veterinary and human medicine. In most species, they are very effective in acute and chronic pains. For example, NSAIDs are often the first drugs used for treatment of pain caused by osteoarthritis in veterinary medicine [20]. In the analgesic study of cats, the effect of flunixin-meglumine (FNX) has been reported in 40 cats undergoing a variety of surgical procedures [9]. It is also well known that NSAIDs cause some adverse effects such as gastrointestinal side-effects in the veterinary medicine. In rats, many kind of NSAIDs have been reported to cause gastrointestinal lesions because of the inhibition of prostaglandins synthesis even new NSAIDs [1]. However, the data on the usage of NSAIDs in cats are less complete than in dogs and, to date, there are no published data about gastrointestinal side-effects in cats.Most NSAIDs are cleared from the body through hepatic metabolism comprising primarily glucuronidation followed by excretion of the resultant polar metabolites via bile and/ or urine. Flunixin is well absorbed from the gastrointestinal tract and undergoes enterohepatic circulation, resulting in a bioavailability of >100% in dogs and cats [16]. At least, two other active transport pathways are invol...

show abstract

“…In support of this, acetaminophen glucuronidation by cat liver microsomes is very slow 29 and acetaminophen glucuronide is a relatively minor metabolite of acetaminophen in cat urine, while it is the main metabolite in dogs and humans (see Figure 4) 5, 30, 31 . As a result acetaminophen clearance is lower, and half-life is longer, in cats (Table 1) resulting in increased circulating levels of acetaminophen, and probably higher p -aminophenol levels in blood.…”

Section: Drug Pharmacokinetic Differences Between Cats Dogs and Humansmentioning

confidence: 78%

“…One of the reasons is that dogs and especially cats show significant methemoglobinemia and other signs of oxidative injury to erythrocytes (Heinz bodies and anemia) following acetaminophen doses that would be considered nontoxic to humans and other species 5, 24 .…”

Section: Drug Pharmacokinetic Differences Between Cats Dogs and Humansmentioning

confidence: 99%

Feline Drug Metabolism and Disposition

Court

2013

Veterinary Clinics of North America: Small Animal Practice

112

View full text Add to dashboard Cite

Synopsis Although it is widely appreciated that cats respond differently to certain drugs when compared with other companion animal species, the causes of these differences are poorly understood. This review critically evaluates published evidence for altered drug effects in cats, focusing on pharmacokinetic differences between cats, dogs and humans, and the molecular mechanisms underlying these differences. Pharmacokinetic studies indicate that acetaminophen, propofol, carprofen, and acetylsalicylic acid (aspirin) are cleared significantly more slowly in cats versus dogs and humans. All of these drugs are metabolized by conjugation. Cats lack the major phenol UDP-glucuronosyltransferase (UGT) enzymes, including UGT1A6 and UGT1A9, that glucuronidate acetaminophen and propofol. Deficient glucuronidation may also explain slower carprofen clearance, although there is no direct evidence for this. However, poor aspirin clearance in cats appears to be mainly a consequence of slower glycine conjugation. Cats are also deficient in several other conjugation enzymes, including N-acetyltransferase (NAT) 2 and thiopurine methyltransferase (TMPT). NAT2 deficiency may be the reason cats are more prone to developing methemoglobinemia rather than hepatotoxicity from acetaminophen. TMPT deficiency may predispose cats to azathioprine toxicity. No evidence was found for slower elimination of drugs cleared by oxidation or unchanged into urine or bile. Piroxicam, an oxidized drug, was cleared much more rapidly in cats than humans and dogs, although the mechanism for this difference is unclear. More work is needed to better understand drug metabolism and disposition differences in cats, thereby enabling more rational prescribing of existing medications, and the development of safer drugs for this species.

show abstract

The toxicity and biotransformation of single doses of acetaminophen in dogs and cats

Cited by 96 publications

References 12 publications

Poisoning of dogs and cats by drugs intended for human use

Poisoning of dogs and cats by drugs intended for human use

Therapeutic and Adverse Effects of Flunixin-Meglumine in Adult and Young Cats

Feline Drug Metabolism and Disposition

Contact Info

Product

Resources

About