Griseofulvin

Brand Names: Fulvicin, Grifulvin V, Grisovin FP, Gristatin, Gris-PEG

Clinical Names: Griseofulvin

Summary

generic name: Griseofulvin

trade name: Fulvicin®, Grifulvin V®, Grisovin FP®, Gristatin®, Gris-PEG®

type of drug: Oral microcrystalline antifungal antibiotic

used to treat: Superficial fungal infections, especially of the scalp and the glabrous skin, caused by those fungi responsible for dermatomycoses in man and animals, namely: M. canis, M. gypseum, M. audouini, E. floccosum, T. tonsurans, T. rubrum, T. mentagrophytes, T. magnini, T. gallinae, T. verrucosum, T. sulfureum, T. interdigitale, T. schoenleini, T. crateriform.

mechanism of action: Griseofulvin works by disrupting spindle and cytoplasmic microtubule function of the fungal microorganisms.

overview of interactions:
• nutrient affecting drug performance and toxicity: Nicotinamide (Vitamin B3)

• nutrient affecting drug performance: Alpha-tocopherol (Vitamin E)

• nutrient affected by drug: Vitamin K

• adverse drug effects: Probiotic Intestinal Flora

• diet affecting drug performance and toxicity: Dietary Fat



Interactions

nutrient affecting drug performance and toxicity: Nicotinamide (Vitamin B3)

• research: In vitro research by Rasool indicates that griseofulvin solubility increased in a nonlinear fashion as a function of nicotinamide concentration. Two aliphatic analogues of nicotinamide (nipecotamide and N,N-dimethylacetamide) were studied as ligands with griseofulvin and were found to increase the solubilities of the drug in a linear fashion.
(Rasool AA, et al. J Pharm Sci 1991 Apr;80(4):387-393.)

• nutritional concern: The simultaneous administration of nicotinamide, a form of vitamin B3, and griseofulvin could result in unintentionally increased levels of the drug. Likewise, use of nicotinamide might enable use of lower dosages of griseofulvin to achieve the same level of therapeutic effect with lower toxic side effects from the drug. Individuals using griseofulvin should avoid supplementing with nicotinamide without consulting with their prescribing physician and/or a nutritionally trained healthcare professional.

nutrient affecting drug performance: Alpha-tocopherol (Vitamin E)

• mechanism: Reduction of P-450 system enzyme activities in the liver achieved with alpha-tocopherol slows down the biotransformation rate of griseofulvin and significantly elevates its blood serum and skin concentrations.
(Lashmanova AP, et al. Vestn Dermatol Venerol 1990;9:15-16.)

• nutritional synergy: Researchers found that by supplementing 50 IU of vitamin E per day in children on griseofulvin blood levels of the drug within four weeks increased enough to allow the drug dose to be reduced by half. While this reduced dose would be beneficial in reducing the drug's side effects, patients prescribed griseofulvin should not supplement with vitamin E or reduce their dosage of the drug without consulting their prescribing physician.
(Mycol Observer. Nov/Dec 1990:8; Leshchenko VM, et al. Vestn Dermatol Venerol. 1988;(12):24-26; Omel'chenko OG. Vestn Dermatol Venerol. 1987;(8):12-15.)

nutrient affected by drug: Vitamin K

• mechanism: Antibiotics destroy all or most of the beneficial bacterial flora that synthesize a high proportion of the body's vitamin K in the gut. Therefore, many antibiotic agents can indirectly cause a depletion of vitamin K.

• nutritional support: Vitamin K1 is available in some multivitamin formulas. Anyone taking antibiotic drugs for more than a few weeks would most likely benefit from supplemental vitamin K, even though it is rare that such a depletion of vitamin K would produce noticeable symptoms.

adverse drug effects: Probiotic Intestinal Flora

• mechanism: As with all antibiotics, the use of this drug may result in an overgrowth of nonsusceptible organisms particularly Monilia (Candida albicans). During the course of eliminating disease-associated organisms, antibiotics also usually destroy normally-occurring beneficial bacterial flora that form an integral part of the healthy intestinal ecology and assist digestive and immune functions. Diarrhea and yeast infections, including vaginal yeast, are common side-effects of the disruption of intestinal ecology and the creation of an environment more susceptible to proliferation of pathogenic levels of opportunistic yeast. In more serious cases, this diminished state of intestinal health can permit overgrowth of C. difficile, a bacteria responsible for pseudomembranous colitis. Patients who develop pseudomembranous colitis as a result of antibiotic treatment can experience diarrhea, abdominal pain, fever, and sometimes even shock. Ultimately, the loss of probiotic flora can contribute to the emergence of an internal environment in the body which eventually may create greater susceptibility to fungal infections. Granulocytopenia, liver damage and other side effects are also possible.

• nutritional support: Supplementation of beneficial probiotic bacterial flora, such as Lactobacillus acidophilus, Bifidobacterium bifidus and Lactobacillus cassei, preferably in the form of a varied, vigorous and abundant culture, will restore the healthy intestinal ecology and stabilize the mucosal lining of the gut. A supplemental dosage of at least one billion organisms per day is necessary to achieve the critical mass of bacterial restoration and successfully reinvigorate healthy intestinal ecology.

diet affecting drug performance and toxicity: Dietary Fat

• mechanism: High-fat meals enhance the absorption of griseofulvin.

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Do not rely solely on the information in this article.

The information presented in Interactions is for informational and educational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, case reports, and/or traditional usage with sources as cited in each topic. The results reported may not necessarily occur in all individuals and different individuals with the same medical conditions with the same symptoms will often require differing treatments. For many of the conditions discussed, treatment with conventional medical therapies, including prescription drugs or over-the-counter medications, is also available. Consult your physician, an appropriately trained healthcare practitioner, and/or pharmacist for any health concern or medical problem before using any herbal products or nutritional supplements or before making any changes in prescribed medications and/or before attempting to independently treat a medical condition using supplements, herbs, remedies, or other forms of self-care.


References

Anonymous. Vitamin E boosts griseofulvin. Mycol Observer. Nov/Dec 1990:8. (Letter)

Becker G. [Foods as interfering factors in pharmacotherapy--shown by various examples]. Med Welt. 1978 Jul 28;29(29-30):1163-1166. (Review) [Article in German]

Fuller R, Gibson GR. Modification of the intestinal microflora using probiotics and prebiotics. Scand J Gastroenterol Suppl 1997;222:28-31.
Abstract: Probiotics and prebiotics modulate the composition of the human gut microbiota. The beneficial effects may result from suppression of harmful microorganisms or stimulation of organisms which contribute in a positive way to the nutrition and health of the host. Both types of supplement represent an attempt to reconstitute the gut flora to its normal composition which has been adversely affected by dietary and environmental stresses.

Kasper H. Protection against gastrointestinal diseases--present facts and future developments. Int J Food Microbiol 1998 May 26;41(2):127-131.
Abstract: The importance of the intestinal microflora and, more specifically its composition, in physiological and pathophysiological processes in the human GIT is becoming more evident. Examples of such processes are translocation, the production and resorption of endotoxins, immune-modulation, and colonic motility. This leads to new possibilities for prevention and therapy of diseases, mainly of the gastrointestinal organs. New discoveries are specifically related to the beneficial effects of lactobacilli which have been discussed for decades. It is possible to increase the proportion of lactobacilli in the gastrointestinal microflora by consumption of fermented dairy products or by oral administration of specific non-digestible substrates such as oligofructose. Results from clinical trials and scientific studies have confirmed the preventive and therapeutic effects of selected strains of lactobacilli in viral- and bacterial-induced intestinal infections, in positively influencing immunological parameters, in normalizing the intestinal motility, and in inhibiting metabolic events in the gut lumen which promote colonic carcinogenesis. Nevertheless, there are still unresolved issues which can only be answered by well designed and well controlled clinical trials.

Lashmanova AP, Omel'chenko OG, Akimov VG. [The dynamics of the griseofulvin levels in the blood and skin of guinea pigs during its combined use with alpha-tocopherol]. Vestn Dermatol Venerol 1990;9:15-16. [Article in Russian]
Abstract: Experiments with 120 guinea pigs have revealed that skin griseofulvin levels depend on blood griseofulvin level and reduce after a prolonged (for 3-4 weeks) administration of the antibiotic in a dose of 30 mg/kg. Reduction of P-450 system enzymes activities achieved with alpha-tocopherol slows down griseofulvin biotransformation rate and significantly elevates its blood serum and skin concentrations.

Leshchenko VM, Omel'chenko OG, Poliakova IIa, Klimova IIa. [Treatment of patients with zooanthroponotic microsporosis with griseofulvin in combination with alpha-tocopherol]. Vestn Dermatol Venerol. 1988;(12):24-26. [Article in Russian]

Omel'chenko OG. [Dynamics of the concentration of griseofulvin in the blood and urine when used jointly with alpha-tocopherol]. Vestn Dermatol Venerol. 1987;(8):12-15. [Article in Russian]

Rasool AA, Hussain AA, Dittert LW. Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. J Pharm Sci 1991 Apr;80(4):387-393.
Abstract: The solubilities of five poorly water-soluble drugs, diazepam, griseofulvin, progesterone, 17 beta-estradiol, and testosterone, were studied in the presence of nicotinamide. All solubilities were found to increase in a nonlinear fashion as a function of nicotinamide concentration. The K1:1 and K1:2 stability constants were as follows: for diazepam, K1:1 = 5.23 M-1 and K1:2 = 8.6 M-2; for griseofulvin, K1:1 = 5.54 M-1 and K1:2 = 8.82 M-2; for progesterone, K1:1 = 5.48 M-1 and K1:2 = 42.47 M-2; for 17 beta-estradiol, K1:1 = 5.38 M-1 and K1:2 = 36.9 M-2; and for testosterone, K1:1 = 5.07 M-1 and K1:2 = 27.47 M-2. Two aliphatic analogues of nicotinamide (nipecotamide and N,N-dimethylacetamide) were studied as ligands with diazepam and griseofulvin and were found to increase the solubilities of both drugs in a linear fashion. The aromatic analogue, N,N-diethylnicotinamide, showed a nonlinear solubilization relationship similar to that seen with nicotinamide. In addition, three other aromatic analogues (isonicotinamide, 1-methylnicotinamide iodide, and N-methylnicotinamide) were studied. These ligands were not soluble enough in water to be studied over the wide range of concentrations used for nicotinamide and N,N-diethylnicotinamide; however, in the concentration range studied, these ligands solubilized diazepam and griseofulvin to a degree similar to that observed with comparable concentrations of nicotinamide. These results suggest that the aromaticity (Pi-system) of the pyridine ring is an important factor in complexation because the aromatic amide ligands were found to enhance the aqueous solubilities of the test drugs to a greater extent than the aliphatic amide ligands.