Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with that with itraconazole

Abstract

Toenail tinea is a very recalcitrant dermatosis. Griseofulvin at 2500 mg/day is the current medication of choice, but it is minimally successful. In a controlled open trial ultramicrosize griseofulvin (UMSG) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients. At 4-week intervals, the patients were evaluated for their clinical and mycological statuses and adverse reactions. Treatment was given for up to 18 months. Compliance was checked by tablet counting. Response (cure, partial cure, marked improvement) was analyzed by the intent-to-treat method. Cured and partially cured patients were followed up. Except for one early dropout, the toenails (mean, 6 to 7) were involved. Cure or partial cure was found in 6% (UMSG at 660 mg), 14% (UMSG at 990 mg), and 19%o (itraconazole at 100 mg) of patients (P = 0.2097); marked improvement was found in 36, 44, and 39%o of patients in the three treatment groups, respectively.Most patients had to be treated for 18 months. Failure was related to short medication periods (adverse drug reactions, dropout). While stable cure was not obtained with UMSG at 660 mg, the higher dose of UMSG and itraconazole gave stable cures in the other patients. Side effects of nausea, diarrhea, and headache were found in 20, 26, and 11 patients, respectively (P = 0.0028), and the numbers in whom medication had to be discontinued differed, too (P = 0.0137). While there was no major difference with glutamic-pyruvic transaminase and -y-GT, total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group (P = 0.0357 and P = 0.0639, respectively, at 3 months). More than 70% of the patients had an average compliance of .90o%; four patients (two dropouts) were poor compliers. In conclusion, it appears questionable whether griseofulvin can continue to be considered the "gold standard" in the treatment of toenail tinea. At present, itraconazole at 100 mg shows better efficacy and is better tolerated.

Collaborative Evaluation of Optimal Antifungal Susceptibility Testing Conditions for Dermatophytes

“…This agrees with previous reports, which showed the efficacy in vitro of this allylamine (3,17,18). However, for ITC we obtained MICs that were within the range of expected concentrations in nail with daily oral doses of 100 to 200 mg (4,19). Similar results were obtained by Korting et al (18), who tested numerous isolates of T. rubrum and T. mentagrophytes from patients with tinea unguium, also by a microdilution method.…”

Oral Treatments for Toenail Onychomycosis

“…* Some authors simply failed to present data for all intended outcomes. 15,36,38 The use of line graphs, means without measures of variance, and P values to present clinical cure data hampered the production of a coherent data summary of clinical cure rates. 13 Only Ling et al, 24 Evans and Sigurgeirsson, 17 and Gupta et al 11 presented data in absolute numbers for clinical cures they defined a priori.…”

“…28,29,36 Two studies with small numbers of patients (N = 80) did not detect a difference in patient outcomes with griseofulvin (500 mg/d) and itraconazole (100 mg/d) taken for 24 to 36 weeks: Walsoe et al 29 found that none of their 19 patients were cured with either drug while the 61 patients in the trial by Piepponen et al 28 had cure rates of 30% in the griseofulvin arm and 36% in the itraconazole arm. Korting et al 36 compared 2 different dosages of griseofulvin (660 mg/d and 990 mg/d) with 100-mg/d dosage of itraconazole taken for 18 months but detected no difference in the cure rates (N = 108).…”

Improving the High Variable Bioavailability of Griseofulvin by SEDDS

“…Because of this 1/3 less ultramicrosize (than microsize) is needed to get the same effect and results. 19,25,26) The dissolution rate of poorly water-soluble drugs often becomes a rate-limiting step in their absorption from the GI tract. 27,28) Various solubilization methods have been used to increase the drug solubility and dissolution properties, including the use of surfactants, water-soluble carriers, polymeric conjugates, particle size reduction, suitable polymorph, anhydrous or organic solvate forms and solid dispersions.…”

“…Ultramicrocrystalline form is administered at doses of 330-990 mg/d. 19) Since the bioavailability of poorly water-soluble drugs can be influenced by interactions with food or by the physicochemical conditions in the gastrointestinal (GI) tract, 20) oral preparation of griseofulvin is commonly prescribed to be administered according to a fixed dosing schedule. The oral bioavailability of griseofulvin is highly variable (25 to 70%).…”