Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 9 SYSTEMIC ANTIFUNGAL THERAPY
soma (Schizotrypanum) cruzi). It is currently in phase
II clinical trials for the treatment of vulvovaginal candidiasis
and phase I trials for the treatment of systemic
mycoses.
GRISEOFULVIN
Griseofulvin, produced by Penicillium griseofulvum, is
a fungistatic drug used to treat dermatophytosis caused
by species of Microsporum and Trichophyton. Although
griseofulvin has traditionally been considered the drug
of choice for systemic therapy of dermatophytosis in
dogs and cats, it has been replaced to some degree by
itraconazole, which is often better tolerated (especially
in cats) and may be more efficacious for the treatment
of M. canis.
Clinical applications
Griseofulvin is indicated and approved in many countries
for systemic treatment of dermatophytic infections
of the skin, hair and claws in dogs and cats.
Mechanism of action
Griseofulvin acts by disrupting mitosis, nucleic acid synthesis
and cell wall synthesis.
Formulations and dose rates
Close monitoring of the complete blood count is important during
griseofulvin administration, especially when using the higher end of
the dose range.
DOGS
Microsize preparation*
• 20–50 mg/kg/day PO divided q.12 h
Ultramicrosize preparation
• 5–20 mg/kg/day PO divided q.12 h
CATS
Microsize preparation*
• 20–50 mg/kg/day PO divided q.12 h
Ultramicrosize preparation
• 5–20 mg/kg/day PO divided q.12 h
* Should be administered with a fatty meal to maximize absorption
Pharmacokinetics
Following absorption from the gastrointestinal tract,
griseofulvin is deposited in the stratum corneum, with
highest concentrations in the outermost layers. Because
it is also deposited in keratin precursor cells, new hair
or nail growth is resistant to infection.
Oral absorption of griseofulvin is limited by its poor
water solubility. However, absorption from the gastrointestinal
tract can be enhanced by administration of
griseofulvin with a fatty meal or as a polyethylene glycol
(PEG) formulation. The particle size of the drug also
affects absorption, with the ultramicrosize formulation
absorbed about 1.5 times as well as the microsized
formulation.
Metabolism of griseofulvin occurs in the liver by
oxidative demethylation and glucuronidation to 6-
desmethylgriseofulvin (an inactive metabolite). Less
than 1% of the drug is excreted unchanged in the
urine.
Adverse effects
● The most common side effects associated with griseofulvin
therapy are vomiting, diarrhea and anorexia.
These can be minimized by decreasing the daily
dose and/or dividing it into two or three
administrations.
● In general, toxicities associated with griseofulvin
administration occur more often in cats than in
dogs.
● Bone marrow suppression (usually manifested as
neutropenia) may occur as an idiosyncratic reaction,
especially in kittens. For this reason, griseofulvin
should not be used in kittens under 8 weeks of age,
with many authors recommending a minimum age
of 12 weeks. In addition, neutropenic reactions are
more common in cats infected with feline immunodeficiency
virus (FIV). Consequently, FIV testing
should be performed prior to initiation of griseofulvin
therapy and cats that are FIV positive should
receive an alternative therapy (such as itraconazole
or terbinafine).
● Other reported side effects of griseofulvin administration
include hepatotoxicity and neurological
signs.
● In general, adverse reactions to griseofulvin therapy
occur more often in Himalayan, Abyssinian, Persian
and Siamese cats than in other breeds.
● Griseofulvin is also a potent teratogen and its use is
contraindicated in pregnant animals or those that
may be bred within a month of therapy. It may also
inhibit spermatogenesis.
Contraindications and precautions
Griseofulvin should not be administered to pregnant
animals, kittens less than 12 weeks of age or cats that
are FIV positive.
Known drug interactions
Phenobarbital may decrease blood concentrations of
griseofulvin by inducing hepatic microsomal enzymes.
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