Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 12 IMMUNOMODULATORY THERAPY
oped illness, with hyperbilirubinemia and elevated
liver enzymes on serum biochemistry.
Known drug interactions
● Danazol should not be administered concurrently
with anticoagulants, as the drug may decrease synthesis
of procoagulant factors by the liver.
● Use in diabetic animals should be undertaken with
care, as danazol may alter insulin requirements via
an effect on carbohydrate metabolism.
● Similarly, care should be taken in patients with
cardiac, renal or hepatic disease.
● Danazol is a teratogen that should not be administered
during pregnancy.
Gold
Clinical applications
Administration of gold salts (chrysotherapy) has found
greatest application in canine medicine in the treatment
of autoimmune disorders, particularly autoimmune
polyarthritis (e.g. rheumatoid arthritis, idiopathic polyarthritis)
and the autoimmune skin diseases (e.g. pemphigus
foliaceus, bullous pemphigoid). In the cat, gold
salts have been used as therapy for pemphigus foliaceus,
chronic gingivostomatitis, plasma cell pododermatitis
and lesions of the eosinophilic granuloma complex. The
majority of reported studies have been with aurothiomalate
rather than auranofin as the latter drug is more
expensive and reportedly less effective.
Mechanism of action
The mechanism of action of gold salts is very poorly
understood, but they are reported to have antiinflammatory,
immunomodulatory, antirheumatic and
antimicrobial effects. Effects on the immune system
include:
● inhibition of lymphocyte proliferation (possibly T-
helper cells)
● inhibition of immunoglobulin production
● inhibition of complement component C1
● inhibition of neutrophil and monocyte-macrophage
function, particularly the release of lysosomal
enzymes and prostaglandins
● inhibition of connective tissue enzymes (elastase,
collagenase, hyaluronidase)
● protection from oxygen radicals.
Formulations and dose rates
Gold salts are available for oral administration as auranofi n (Ridaura®;
3 mg tablets containing 29% gold) or in an injectable form as aurothiomalate
(Myocristin®; 20, 40 or 100 mg/mL suspension containing
50% gold). These drugs are not currently licensed for companion
animal use.
DOGS
• Auranofi n has been administered to dogs at a dose of 0.05–
0.2 mg/kg q.12 h PO, with a maximum daily dose of 9 mg/day
• Aurothiomalate is administered to dogs under 10 kg bodyweight
by deep IM injection using a dosage regimen of 1 mg in week
1, 2 mg in week 2 and then 1 mg/kg every 7–28 days
• For a dog of over 10 kg bodyweight, the recommendation is
5 mg in week 1, 10 mg in week 2 (to a maximum of 1 mg/kg)
and then 1 mg/kg every 7–28 days
CATS
• IM aurothiomalate is given, using the protocol described above
for smaller dogs. The drug has a slow onset of action and
administration for 6–12 weeks may be required before clinical
benefi t is observed. Because of this, many clinicians advocate
the use of low-dose glucocorticoids (e.g. prednisolone 1–2 mg/
kg q.12–48 h PO) during the initial phase of treatment
• Once disease remission is achieved, the dose or dosage interval
should be reduced where possible
Pharmacokinetics
Following oral administration, gold is absorbed from
the intestine (approximately 20–25% of the gold content
of the drug) and binds plasma proteins with moderate
affinity. Gold particularly concentrates within liver,
kidney, spleen, lungs and adrenal glands. At the cellular
level, gold also accumulates predominantly within macrophages.
Approximately 60% of the absorbed dose is
excreted in urine and unabsorbed gold is excreted in the
feces.
After IM injection, gold is rapidly absorbed, with
peak serum concentrations achieved in 4–6 h and up to
95% of the agent is bound to plasma proteins. The
half-life in blood is approximately 6 d. The drug is predominantly
concentrated in the synovium, with lower
levels in liver, kidney, spleen, bone marrow, adrenals
and lymph nodes. Approximately 70% of the absorbed
dose is excreted in urine and the remainder is lost in the
feces.
Adverse effects
● Gold salts are contraindicated in patients with SLE,
diabetes mellitus or hematological, hepatic, renal or
cardiac disease.
● Recorded adverse effects include diarrhea (more
commonly with auranofin than aurothiomalate),
blood dyscrasias (especially thrombocytopenia,
hemolytic anemia, leukopenia), hemorrhage or ulceration
of mucous membranes, mucocutaneous disease
of the erythema multiforme–toxic epidermal necrolysis
spectrum, encephalitis, neuritis, hepatotoxicity or
renal disease (damage to proximal tubules).
● Nephrotoxic effects are particularly marked in cats
and may lead to proteinuria.
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