GRISEOFULVIN (MICROSIZE), GRISEOFULVIN (ULTRAMICROSIZE)

Chemistry - A fugistatic antibiotic produced by species of Penicillium (primarily P. griseofulvum), griseofulvin occurs as an odorless or nearly odorless, bitter tasting, white to creamy white powder.
It is very slightly soluble in water and sparingly soluble in alcohol.
Two forms of the drug are available commercially. Microsize griseofulvin contains particles with apredominant size of 4 µm in diameter, while the ultramicrosize form particle size averages less than1 micron in diameter.

Storage, Stability, Compatibility

Although griseofulvin is relatively thermostable, productsshould be stored at less than 40°C, preferably at 15-30°C. Griseofulvin suspension should bestored in tight, light-resistant containers. Microsize tablets and capsules should be stored in tightcontainers; the ultramicrosize tablets should be stored in well-closed containers.

Pharmacology - GRISEOFULVIN (MICROSIZE), GRISEOFULVIN (ULTRAMICROSIZE)

Griseofulvin acts on susceptible fungi by disrupting the structure of the cell'smitotic spindle, thereby arresting the metaphase of cel division. Griseofulvin has activity againstspecies of Trichophyton, Microsporum and Epidermophyton. Only new hair or nail growth is resistant to infection. It has no antibacterial activity, and is not clinically useful against otherpathogenic fungi.
Uses, Indications - In veterinary species, griseofulvin is approved for use in dogs and cats to treatdermatophytic fungal (see above) infections of the skin, hair and claws, and to treat ringworm(caused by T. equinum and M. gypseum) in horses. It has also been used in laboratory animals andruminants for the same indications.

Pharmacokinetics - GRISEOFULVIN (MICROSIZE), GRISEOFULVIN (ULTRAMICROSIZE)

The microsized form of the drug is absorbed variably (25-70%); dietary fatwill enhance absorption. The ultramicrosize form of the drug may be nearly 100% absorbed.
Generally, the ultramicrosize form is absorbed 1.5 times as well as the microsized form for a givenpatient.
Griseofulvin is concentrated in skin, hair, nails, fat, skeletal muscle and the liver, and can be foundin the stratum corneum within 4 hours of dosing.
Griseofulvin is metabolized by the liver via oxidative demethylation and glucuronidation to 6-desmethylgriseofulvin which is not active. In humans, the half-life is 9-24 hours. A serum half-lifeof 47 minutes has been reported for dogs. Less than 1% of the drug is excreted unchanged in theurine.

Contraindications, Precautions, Reproductive Safety

Griseofulvin is contraindicated in patients hypersensitive to it or with hepatocellular failure.
Because kittens may be overly sensitive to the adverse effects associated with griseofulvin, theyshould be monitored carefully if treatment is instituted.
Griseofulvin is a known teratogen in cats. Dosages of 35 mg/kg given to cats during the firsttrimester caused cleft palate, and other skeletal and brain malformations in kittens. Griseofulvin mayalso inhibit spermatogenesis. Because dermatophytic infections are not generally life-threateningand alternative therapies are available, use of the drug should be considered contraindicated duringpregnancy.

Adverse Effects, Warnings

Griseofulvin can cause anorexia, vomiting, diarrhea, anemia, neutropenia, leukopenia, depression, ataxia, hepatotoxicity or dermatitis/photosensitivity. With theexception of GI symptoms, adverse effects are uncommon at usual doses. Cats, particularly kittens, may be more susceptible to adverse effects than other species. This could be due to this species'propensity to more slowly form glucuronide conjugates and thus metabolize the drug at a slowerrate than either dogs or humans.
Overdosage, Acute Toxicity - No specifics regarding griseofulvin overdosage or acute toxicitywas located. It is suggested that significant overdoses be handled with gut emptying, charcoal andcathartic administration unless contraindicated. Contact a poison control center for more information.
Horses have received 100 mg/kg PO for 20 days without apparent ill effect.

Drug Interactions

Phenobarbital (and other barbiturates) has been implicated in causing decreased griseofulvin blood concentrations, presumably by inducing hepatic microsomal enzymesand/or reducing absorption. If phenobarbital and griseofulvin are given concurrently, griseofulvindosage adjustment may be necessary.
Coumarin (e.g., warfarin) anticoagulants may have their anticoagulant activity reduced bygriseofulvin; anticoagulant adjustment may be required.
Griseofulvin may potentiate the effects of alcohol.