Griseofulvin

Pharmacokinetics

Griseofulvin is commercially available for oral administration as griseofulvin microsize (4 μm particle size) and griseofulvin ultramicrosize (1 μm particle size). The oral availability of the micronized formulation is variable, 25–70%; ultramicronized griseofulvin, in contrast, is almost completely absorbed [ ]. Peak plasma concentrations occur about 4 hours after dosing. Griseofulvin distributes to keratin precursor cells and is concentrated in skin, hair, nails, liver, adipose tissue, and skeletal muscle. In skin, a concentration gradient is established over time, with the highest concentrations in the outermost stratum corneum [ , ]. However, within 48–72 hours after withdrawal, plasma concentrations of griseofulvin are markedly reduced and it is no longer detectable in the stratum corneum [ ]. The half-life of griseofulvin is 9–21 hours [ ]. It is oxidatively demethylated and conjugated with glucuronic acid, primarily in the liver; its major metabolite, 6-desmethylgriseofulvin, is microbiologically inactive [ ]. Within 5 days, about one-third of a single dose of micronized griseofulvin is excreted in the feces, and 50% in the urine, predominantly as glucuronidated 6-desmethylgriseofulvin [ , ]. The slow penetration rate of griseofulvin into tissues may explain difficulties and delays in eradication of infection in nails [ ].

General adverse effects and adverse reactions

The more common adverse reactions to griseofulvin include headache and a variety of gastrointestinal symptoms. Griseofulvin can cause photosensitivity and exacerbate lupus and porphyria. Cases of erythema multiforme-like reactions, toxic epidermal necrolysis, and a reaction resembling serum sickness have been reported. Proteinuria, nephrosis, hepatotoxicity, leukopenia, menstrual irregularities, estrogen-like effects, and reversible impairment of hearing have been reported rarely [ , ]. Griseofulvin is teratogenic in animals and has mutagenic and carcinogenic potential, but the significance of these observations for humans is unclear [ ].

Nervous system

Headache is the most common adverse effect of griseofulvin [ ]. It occurs in about 50% of patients and can be severe. Drowsiness, dizziness, fatigue, confusion, depression, irritability, and insomnia have also been observed [ ]. Impaired co-ordination and unsteadiness while walking have been reported in some cases when there was confusion [ ]. Peripheral neuritis has been attributed to griseofulvin, but with little proof of a causal relation [ ].

Sensory systems