Oral Administration Of Griseofulvin Research Articles

The kerion: an angry tinea capitis.

Tinea capitis has a high incidence with a global changing pathogen distribution, making this condition a public health concern around the world. As the infection is initially asymptomatic, it is easily spread. Moreover, it is present in many fomites, including hairbrushes, pillows, and bedding. Prompt recognition and treatment is necessary for kerion, an inflammatory subtype characterized by tender boggy plaques with purulent drainage. Kerion is usually associated with infection by zoophilic dermatophytes, although other sources have been described. Treatment for this severe form of dermatophytic infection can be challenging. In addition to the use of topical treatments, oral administration of griseofulvin, terbinafine, itraconazole, or fluconazole is often required. Griseofulvin, the first-line treatment, may not completely eradicate pathogen colonization of the host and may contribute to reinfection and prevalence of infective but asymptomatic carriers. This review highlights new agents that are being evaluated for the treatment of kerion and typical tinea capitis, enhanced diagnostic criteria, and a grading system for kerion evaluation.

In vitro/ in vivo phototoxic risk assessments of griseofulvin based on photobiochemical and pharmacokinetic behaviors

The present investigation aims to establish efficacious screening strategy to clarify the phototoxic potential of pharmaceutical substances and its possible pathways by characterizing both photobiochemical properties and pharmacokinetic profiles. Photochemical behavior of griseofulvin, as model compounds, was evaluated by reactive oxygen species (ROS) assay, and the photogenotoxic potential was also assessed by DNA binding assay, DNA photocleavage assay, and atomic force microscopy. Pharmacokinetic (PK) study was also carried out after dermal and oral administration of griseofulvin in rats. ROS assay suggested the phototoxic potential of griseofulvin via type II photochemical pathways, and the photogenotoxic risk of griseofulvin was also proposed as evidenced by high affinity toward DNA and potent DNA photocleaving activity. PK profiling and in vivo phototoxicity testing demonstrated that a highly concentrated griseofulvin in the skin might cause phototoxic skin reactions in rats, whereas oral administration of griseofulvin in single dosing regimen (20 mg/kg) resulted in 10 3-fold less skin deposition than phototoxic skin concentration of griseofulvin. Upon these findings, the phototoxic potential of griseofulvin might not be severe at least in a single oral dosing regimen, whereas it might be phototoxic in dermal administration. The combination use of photobiochemical and pharmacokinetic data would be valuable to provide reliable prediction on phototoxic risk and possible toxic pathways of new drug entities in the early stage of drug discovery.

Evaluation of in vivo dissolution behavior and GI transit of griseofulvin, a BCS class II drug

Mean plasma concentration–time profile of griseofulvin, a BCS class II drug, orally administered as powders into rats, was predicted based on GITA model. However, it was very difficult to predict the individual plasma profile because of large inter-individual difference. As the absorption of griseofulvin would be rate-limited by the dissolution process, we tried to analyze the in vivo dissolution kinetics of griseofulvin by focusing on gastric emptying and intestinal transit as physiological factors influencing the in vivo dissolution kinetics. After oral administration of griseofulvin, theophylline and sulfasalazine into rats, gastric emptying and intestinal transit were simultaneously estimated by analyzing the absorption kinetics of theophylline and observing the appearance of sulfapyridine in plasma, respectively. Gastric emptying kinetics was not significantly correlated with absorption or dissolution behavior of griseofulvin. On the other hand, the cecum-arriving time reflecting the intestinal transit was significantly correlated with both AUC and total dissolved amount of griseofulvin. T max of griseofulvin also increased with the increase of cecum-arriving time. These results clearly indicate that the longer residence time could lead to the higher dissolution and absorption of griseofulvin and that the variance of intestinal transit could be responsible for the inter-individual difference of the in vivo absorption behavior.

Current topics in diagnosis and treatment of tinea unguium in Japan.

The number of patients with tinea unguium accounts for 0.5% to 2% of the total number of outpatients in Japan. The diagnosis of tinea unguium can be relatively easily made on the basis of clinical symptoms and direct microscopic findings. However onychomycosis due to fungi other than dermatophytes should always be suspected if no dermatophytes are cultured despite positive findings in direct microscopy. In such cases, it is necessary to repeat cultures and conduct histopathological evaluation using PAS-staining technique or enzyme antibody technique. At present, oral administration of griseofulvin and terbinafine are the treatments covered by health insurance in Japan. In the future, however, other orally active antifungal drugs such as itraconazole and fluconazole will become available for use by in-patients who do not respond to griseofulvin. It is essential to patiently continue treatment even if oral therapy is impossible, because other therapies such as ODT therapy using topical antifugal agents and urea ointment or abrading affected nails as much as possible with a file or dental drill may be effective without oral therapy.

An experimental model for evaluation of antifungal agents in a Trichophyton mentagrophytes infection of guinea pigs.

A Trichophyton mentagrophytes infection of guinea pigs induced by an occlusive procedure is described. The method of evaluation permits comparison of efficacy of antifungal agents which are not tested simultaneously. Activity was demonstrated following topical application of clotrimazole, miconazole, tolnaftate or griseofulvin and oral administration of griseofulvin. Oral ketoconazole had little effect in this dermatophyte model.

Simultaneous determination of griseofulvin and 6-desmethylgriseofulvin in plasma by electron-capture gas chromatography.

Two methods have been developed for the simultaneous determination of griseofulvin and its major metabolite 6-desmethylgriseofulvin in plasma using electron-capture gas chromatography. The first method was based on the quantitative reversion of the 6-desmethyl metabolite to griseofulvin by diazomethane. Plasma extract was chromatographed both before and after treatment with diazomethane, the former being the measure of griseofulvin and the latter representing the sum of the two compounds. In the second method, plasma extract was treated with diazobutane and griseofulvin and the butylated metabolite were separated by gas chromatography. The sensitivity for griseofulvin was 20 ng/ml by both methods and that for the metabolite was 20 ng/ml and 40 ng/ml by the first and the second method, respectively. The concentrations of the metabolite as well as griseofulvin were determined in dog and human plasma after oral administration of griseofulvin.

Cutaneous Mycosis Caused by Paecilomyces lilacinus

A 20-year-old woman had erythematous scaly plaques persistent for 15 years on the left cheek. Cultures from scales and biopsy specimens on Sabouraud's glucose agar repeatedly yielded floccose lilac colonies, and those on a Czapek's solution agar plate developed deep purplish red pigment, which is characteristic of Paecilomyces lilacinus. The PAS stain of the tissue section showed ovoid, divergent, or club-shaped fungal elements among the inflammatory cells or in giant cells. Two months after the patient and a control subject were inoculated with the isolates, P lilacinus could be reisolated from the patient only. Oral administration of griseofulvin significantly reduced erythema and papules. This is the first report, to our knowledge, of deep cutaneous mycosis caused by P lilacinus.

Experiences in one hundred thirty-seven patients treated with oral griseofulvin. Special reference to clinical recurrences. the healthy carrier state, and their management.

Shortly after the original publication of Gentles 1 on the effectiveness of griseofulvin in Trichophyton infections of laboratory animals, numerous investigators have reported on striking clinical results obtained with the oral administration of griseofulvin in treatment of superficial dermatomycoses in man. Williams et al., 2 Riehl, 3 Blank and Roth, 4 and Pardo-Castello 5 were among the first attempting such clinical studies. A main purpose of this paper is to evalu ate the recurrences noted in patients either after completion of a course of oral therapy with griseofulvin or in evidence during the course of treatment . The management of these cases will be discussed. Several patients, moreover, were found to have persistently positive mycological laboratory findings despite apparent clinical cure. This situation we have designated as the healthy carrier state. Method We wish to call attention to the fact that our studies commenced in the winter months and extended into

Severe reaction to griseofulvin.

The successful systemic treatment of several types of superficial mycoses in humans by the oral administration of griseofulvin was recently described by Blank and Roth. 1 Adverse reactions after the administration of this drug, in commonly used doses, have in general, been of slight import. Moreover, the maximum side-effects, including malaise, headache, mild gastrointestinal disturbances, evanescent leukopenia, and insignificant macular and papular eruptions, reportedly vanished promptly on discontinuation of the drug therapy. The following report describes a severe generalized angioneurotic edema and persistent urticaria which occurred after griseofulvin therapy. This reaction was, in its clinical manifestations and in its response to therapy, an exact counterpart of the severe type of sensitivity reaction seen after the intramuscular administration of penicillin. Report of a Case A man aged 30 was under treatment for a typical hypertrophic lichen planus with intravenous injections of cyanocobalamin. On Dec. 16,1958, he noted a flat, red, circinate,

Presence of griseofulvin in hair of guinea pigs after oral administration.

GENTLES1 has found that oral administration of griseofulvin to guinea pigs previously infected with either Microsporum canis or Trichophyton mentagrophytes arrests the progress of the fungal disease and prevents the highly inflammatory reaction normally encountered in untreated animals. Histological examination showed that most of the hair follicles and most of the lower portions of hair-shafts were free from dermatophytes after a few oral doses of the antibiotic. The hyphal tips of the fungi were sometimes malformed and in that way reminiscent of the effect of griseofulvin on other susceptible fungi.