グリセオフルビン

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

LogP = 2.18

2

STOUT OCTAHEDRA OR RHOMBS FROM BENZENE

WHITE TO CREAMY POWDER

COLORLESS CRYSTALLINE SOLID

less than 1 mg/mL at 70 °F (NTP, 1992)

SOL IN N,N-DIMETHYLFORMAMIDE @ 25 °C: 12-14 G/100 ML; SLIGHTLY SOL IN ETHANOL, CHLOROFORM, METHANOL, ACETIC ACID, ACETONE, BENZENE, & ETHYL ACETATE; PRACTICALLY INSOL IN WATER & PETROLEUM ETHER

5.04e-02 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antifungal medicines

428 °F (NTP, 1992)

220 °C

220 °C

SPECIFIC OPTICAL ROTATION: +370 DEG @ 17 °C/D (SATURATED CHLOROFORM SOLN)

MAX ABSORPTION (ALCOHOL): 291 NM (LOG E= 4.37); 325 NM (LOG E= 3.77); SPECIFIC OPTICAL ROTATION: +337 DEG @ 21 °C/D (ACETONE)

This chemical does not meet GHS hazard criteria for 0.7% (1 of 149) of reports.

Danger

H317 (90.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P261, P272, P280, P302+P352, P318, P321, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 149 reports by companies from 15 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

Hazard Traits - Carcinogenicity

Griseofulvin: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this compound may include urticaria, headaches, confusion, dizziness, nausea, diarrhea, photosensitivity and leukopenia. Other symptoms may include epigastric distress, fever and arthralgia. It may cause renal damage and porphyria. It may also cause peripheral neuritis, syncope and blurred vision. Exposure has caused skin rashes, fatigue, proteinuria and, rarely, angioneurotic edema, paresthesia and lupus erythematosus. Symptoms may include dryness of the mouth, an altered sensation of taste, gastrointestinal disturbances, severe allergic reactions, erythema multiforme, exfoliative dermatitis, candidiasis, depression, irritability and, rarely, hepatitis. Other symptoms reported are oral thrush, vomiting, insomnia, impairment of the performance of routine activities and, rarely, lupus-like syndromes and granulocytopenia. Skin irritation may occur. Exposure can lead to lethargy, vertigo, transient macular edema, augmentation of the effects of alcohol, heartburn, flatulence, angular stomatitis, neutropenia, punctate basophilia, monocytosis, albuminuria, cylindruria and hepatotoxicity. Abnormalities of the sexual organs and breasts have occurred, especially in children. It is contra-indicated in persons with porphyria and liver failure. A case of blurred vision with greenish tint, and papilledema have been reported.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

LIN C, SYMCHOWICZ S; ABSORPTION, DISTRIBUTION, METABOLISM, & EXCRETION OF GRISEOFULVIN IN MAN & ANIMALS; DRUG METAB REV 4(1) 75 (1975). PHARMACOKINETICS, METABOLISM & DISTRIBUTION OF GRISEOFULVIN IN MAN & ANIMALS ARE REVIEWED.

DE MATTEIS F; HEPATIC PORPHYRIAS CAUSED BY 2-ALLYL-2-ISOPROPYLACETAMIDE, 3,5-DIETHOXYCARBONYL-1,4-DIHYDROCOLLIDINE, GRISEOFULVIN & RELATED COMPD; HANDB EXP PHARMAKOL 44 (HEME HEMOPROTEINS) 129 (1978). A REVIEW & DISCUSSION WITH MANY REF OF THE INTERACTIONS OF THE ABOVE WITH LIVER PORPHYRIN METAB.

DAVIES RR; ANTIFUNGAL CHEMOTHERAPY. GRISEOFULVIN; ANTIFUNGAL CHEMOTHER 149 (1980). A REVIEW WITH MANY REF ON THE PHARMACOLOGY AND TOXICOLOGY OF GRISEOFULVIN.

Skin Sens. 1 (90.6%)

Germ cell mutagenicity - Category 1B

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Griseofulvin preparation should generally be stored at a temperature less than 40 degrees C, preferably between 15-30 degrees C; microsize griseofulvin oral suspension should be protected from freezing and stored in light-resistant containers. ... Should be stored in well-closed containers.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for GRISEOFULVIN (9 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

...METABOLISM /OF GRISEOFULVIN/ IS ACCELERATED BY...PRIMIDONE IN RATS AND MAN...

GRISEOFULVIN ACTED AS A COCARCINOGEN WITH SKIN APPLICATIONS OF 3-METHYLCHOLANTHRENE IN MICE...

Effects may be potentiated when alcohol is used concurrently with griseofulvin; also, concurrent use with griseofulvin may result in tachycardia, diaphoresis, and flushing.

/Coumarin- or indandione-derivative anticoagulants/ effects, may be decreased when these agents are used concurrently with griseofulvin; decrease is thought to be due to accelerated metabolism of anticoagulants secondary to stimulation of hepatic microsomal enzyme activity; prothrombin time should be monitored until a stable level is maintained; dosage adjustments may be necessary during and after griseofulvin therapy.

For more Interactions (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page.

Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with griseofulvin, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. Clinically apparent hepatotoxicity is rare and only isolated case reports have been published. The liver injury is typically cholestatic and usually arises within the first few months of therapy. Signs of hypersensitivity such as fever, rash and eosinophilia are rare but griseofulvin can include hypersensitivity reactions and at least one case of DRESS syndrome accompanied by serum aminotransferase elevations has been reported with its use. Published cases of griseofulvin induced liver injury have all been self-limited, recovery requiring 1 to 3 months. Griseofulvin can increase intrahepatic levels of protoporphyrin and induce acute attacks of porphyria in patients with acute intermittent porphyria in remission.

Overall, griseofulvin has few adverse effects. It most commonly causes gastrointestinal issues of nausea, vomiting, and diarrhea, as well as headaches and allergic reactions. Other adverse effects include photosensitivity, fixed drug eruption, petechiae, pruritus, and urticaria. It may cause a worsening of lupus or porphyria.

Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

PHOTOSENSITIVITY & PPT OF DISCOID LUPUS ERYTHEMATOSUS IN 1 PT WITH NO PREVIOUS EVIDENCE OF THE DISEASE; IN ANOTHER PT WITH KNOWN SYSTEMIC LUPUS ERYTHEMATOSUS FEVER & MALAISE AFTER TREATMENT WITH GRISEOFULVIN.

THE OCCURRENCE OF CHOLESTATIC JAUNDICE IN PT RECEIVING GRISEOFULVIN IS DESCRIBED. COMPLETE RECOVERY FOLLOWED DISCONTINUATION OF DRUG ADMIN.

Griseofulvin

Group 2B: Possibly carcinogenic to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

2001

2000

2B, possibly carcinogenic to humans. (L135)

Drug Induced Liver Injury Rank (DILIrank 2.0)

Griseofulvin

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

...IT INTERFERES WITH CHITIN DEVELOPMENT IN MOSQUITO LARVAE.

TERATOGENIC ACTIVITY WAS OBSERVED MOST OFTEN WHEN PREPN WAS APPLIED ON 8TH-9TH DAY OF PREGNANCY. MALFORMATIONS OR SKELETON WERE DEMONSTRATED IN 46% OF FETUSES FOLLOWING AN ORAL 5 G/KG DOSE.

PHOTOSENSITIZING WAS STUDIED IN MICE BY A QUANTITATIVE IN VIVO METHOD. PHOTOTOXICITY IN VIVO, HITHERTO NOT DEMONSTRATED, WAS OBSERVED WITH GRISEOFULVIN.

FEEDING MICE GRISEOFULVIN INCR LIVER WT TO 9% OF BODY WT WITH PROPORTIONAL DECR IN MICROSOMAL PROTEIN/G LIVER WET WT. CYTOCHROME P-450 & B5 CONTENT WAS 50% & 200% OF THAT IN CONTROL MICROSOMES.

For more Non-Human Toxicity Excerpts (Complete) data for GRISEOFULVIN (21 total), please visit the HSDB record page.

Evaluation: There is inadequate evidence in humans for the carcinogenicity of griseofulvin. There is sufficient evidence in experimental animals for the carcinogenicity of griseofulvin. Overall evaluation: Griseofulvin is possibly carcinogenic to humans (Group 2B).

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

D - Dermatologicals

D - Dermatologicals

QD - Dermatologicals

QD - Dermatologicals

D01BA01

Griseofulvin is a mycotoxic metabolic product of <i>Penicillium spp.</i> It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis.

Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis.

Fungistatic; griseofulvin inhibits fungal cell mitosis by causing disruption of the mitotic spindle structure, thereby arresting the metaphase of cell division. It is deposited in varying concentrations in the keratin precursor cells of skin, hair, and nails, rendering the keratin resistant to fungal invasion. As the infected keratin is shed, it is replaced with healthy tissue.

9-21 hours

DRUG HAS A HALF-LIFE IN PLASMA OF ABOUT 1 DAY, & APPROX 50% OF ORAL DOSE CAN BE DETECTED IN THE URINE WITHIN 5 DAYS, MOSTLY IN THE FORM OF METABOLITES /SRP: 36% IN THE FECES WITHIN 5 DAYS/.

The half-life of griseofulvin in canine plasma was found to be 47 minutes ... .

Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate.

Griseofulvin is mainly metabolized to 6-dimethylgriseofulvin and its glucuronide.

...IT HAS BEEN REPORTED THAT 6-DEMETHYLGRISEOFULVIN IS THE MAJOR URINARY METABOLITE...IN MAN, THE PREVIOUSLY REPORTED 4-DEMETHYL-GRISEOFULVIN WAS ABSENT. GRISEOFULVIC ACID (7-CHLORO-4,6-DIMETHOXY-6'-METHYLGRISAN-2',3,4'-TRIONE) WAS IDENTIFIED...

Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate. Half Life: 9-21 hours

32HRV3E3D5

GRISEOFULVIN

Physiologic Effects [PE] - Decreased Mitosis

Physiologic Effects [PE] - Microtubule Inhibition

Established Pharmacologic Class [EPC] - Tubulin Inhibiting Agent

Griseofulvin is a Tubulin Inhibiting Agent. The physiologic effect of griseofulvin is by means of Decreased Mitosis and Microtubule Inhibition.

Poorly absorbed from GI ranging from 25 to 70% of an oral dose. Absorption is significantly enhanced by administration with or after a fatty meal.

IN RATS GIVEN ORAL DOSES OF 100 MG/KG BODY WT (36)CL-GRISEOFULVIN, 10% OF ACTIVITY WAS FOUND IN URINE AFTER 24 HR & 4% DURING 24-48 HR. ...IN ANOTHER STUDY, WITHIN 24-HR PERIOD ONLY 0.14% OF SIMILAR ORAL DOSES IN RATS WAS FOUND IN URINE, & 16% WAS RECOVERED IN FECES. FOLLOWING ITS IV INJECTION GRISEOFULVIN WAS DISTRIBUTED EVENLY THROUGHOUT TISSUES, ALTHOUGH HIGHER LEVELS WERE FOUND IN SKIN & LUNG.

Microsize - variable, ranging from 25 to 70% of an oral dose. Ultramicrosize - Almost completely absorbed. Absorption is significantly enhanced by administration with or after a fatty meal.

Griseofulvin is deposited in varying concentrations in the keratin layer of the skin, hair, and nails. It can be detected in the stratum corneum of the skin within a few hours following administration. Only a very small fraction of an oral dose is distributed in the body fluids and tissues.

Elimination: Renal. less than 1% of a dose is excreted as unchanged drug in the urine. Approximately 36% of griseofulvin is excreted unchanged in the feces.

GRISEOFULVIN IS PROBABLY DEPOSITED IN BASAL CELLS AND IS CARRIED OUTWARDS INTO EPIDERMIS AS NORMAL SKIN GROWTH PROCEEDS. THIS...MAKES FOR LONG LATENCY FROM TIME MEDICATION IS BEGUN UNTIL EVIDENCE OF IMPROVEMENT OCCURS.

MEDICATION (VET)

MEDICATION

Use (kg; approx.) in Germany (2009): >250

Griseofulvin is used both in animals and in humans, to treat fungal infections of the skin (commonly known as ringworm) and nails. Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. Griseofulvin is reserved for cases with nail, hair or large body surface involvement. (Wikipedia)

ANTIBIOTIC SUBSTANCE PRODUCED BY PENICULLIUM GRISEOFULVUM DIERCKX AND BY P. JANCZEWSKII ZAL. (= P. NIGRCANS (BANIER) THOM.). ISOLATION: OXFORD ET AL, BIOCHEM J 33, 240 (1939); BRIAN ET AL, TRANS BRIT MYCOL SOC 29, 173 (1946); HOCKENHULL, DOREY ET AL, US PATENT 3,069,328-9 (1962 TO GLAXO).

DUSTS 1.5-3.5% WT/WT FOR USE AT 75 LB/ACRE. WETTABLE POWDERS, DISPERSIBLE CONCENTRATES (SOLN IN DIMETHYL FORMAMIDE WITH DISPERSING AGENT). /SRP: NOT APPROVED FOR USE ON CROPS IN US./

GRISEOFULVIN, USP (FULVICIN U/F, GRIFULVIN V, GRISACTIN), IS MARKETED IN CAPSULES CONTAINING 125 OR 250 MG & IN TABLETS CONTAINING 125, 250, OR 500 MG; IT IS ALSO AVAIL AS ORAL SUSPENSION (125 MG/5 ML). ... TABLETS INCORPORATING ULTRAMICROSIZED PREPN (FULVICIN P/G, GRIS-PEG) CONTAIN 125 OR 250 MG OF GRISEOFULVIN (EQUIVALENT TO 250 OR 500 MG OF PREPN...ABOVE).

BIOAVAILABILITY OF A 500 MG MICROSIZE FORMULATION WAS COMPARED TO 2 NEW ULTRAMICROSIZE FORMULATIONS. ONE 330 MG ULTRAMICROSIZE TABLET IS BIOEQUIVALENT TO 2 165 MG ULTRAMICROSIZE TABLETS & EITHER ULTRAMICROSIZE DOSAGE REGIMEN IS BIOEQUIVALENT TO 500 MG OF THE MICROSIZE FORMULATION.

THE BIOAVAILABILITY OF GRISEOFULVIN TABLETS SPRAY DRIED WITH 20% METHYLCELLULOSE WAS DETERMINED IN 10 RABBITS. COMPARED TO REGULAR TABLETS, DRUG ABSORPTION WAS GREATER IN THE SPRAY DRIED PREPN.

Tablet, 250 mg, 500 mg; suspension, 250 mg/ml /Grifulvin V/