Studies on the Biological Disposition of Griseofulvin, an Oral Antifungal Agent

Bedford, Carole; Busfield, Dorothy; Child, Korean J; Gregor, I. Mac; Sutherland, Patricia; Tomich, E. G.

doi:10.1001/archderm.1960.03730050091016

Cited by 56 publications

(6 citation statements)

References 3 publications

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“…Tromexan (2 1) and griseofulvin (34) also have this rare pharmacologic property. Tromexan is a 4-hydroxycoumarin and has low aqueous solubility (35).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Coumarin Anticoagulant Drugs : A Comparison of the Pharmacodynamics of Dicumarol and Warfarin in Man

O’Reilly¹,

Aggeler²,

Leong³

1964

Thromb Haemost

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SummaryThe pharmacodynamic and prothrombinopénie effects of the coumarin anticoagulant drugs warfarin and dicumarol were compared in man by means of specific chemical assays for the drugs and the Quick prothrombin time for the response. The absorption of warfarin was rapid and complete, and the prothrombinopénie response was similar after administration by any route. Absorption of dicumarol as a solution or powder was rapid while as whole tablets it was often slow. Dicumarol in solution taken orally produced higher maximum concentrations of drug in plasma, more rapid absorption rates, less unchanged drug in stool and an earlier and greater prothrombin complex response than the tablets. Only a slight effect was produced by varying the formulation of warfarin. In all subjects 15 to 30% of the oral dose of dicumarol was recovered as unchanged drug in the stool. Unchanged warfarin was not recovered from the stool in any experiment.The apparent volume of distribution (Vd) for warfarin and high doses of dicumarol was about 12.5% of body weight, approximately the size of the albumin space. The long half-time of disappearance (t½) of both drugs, their prolonged duration of action, small volume of distribution, and lack of excretion of unchanged drug in the urine are probably related to their high degree of binding to plasma proteins. The t½ and Vd for warfarin are independent of dose size; the unusual dependency of these parameters on dose size with dicumarol suggests tissue uptake, perhaps by the reticuloendothelial system.A good correlation was found between the t½ of warfarin and dicumarol and the magnitude and duration of response. Up to a certain point increasing the dose of these drugs hastened the occurrence of hypoprothrombinemia ; beyond a dose size characteristic for each individual no further hastening could be obtained.A substance extracted from the stool of subjects receiving dicumarol intravenously and orally is probably a metabolite of the drug.

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“…Tromexan (2 1) and griseofulvin (34) also have this rare pharmacologic property. Tromexan is a 4-hydroxycoumarin and has low aqueous solubility (35).…”

Section: Discussionmentioning

confidence: 99%

Studies on the Coumarin Anticoagulant Drugs : A Comparison of the Pharmacodynamics of Dicumarol and Warfarin in Man

O’Reilly¹,

Aggeler²,

Leong³

1964

Thromb Haemost

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“…In contrast, the absorption profiles of the bipyramidal particles were erratic and absorption was not completed by 24 h, which suggested a slow, discontinuous dissolution of the bipyramidal particles in the rat gastrointestinal tract. Griseofulvin is known to be absorbed primarily in the duodenum, and to a smaller extent from the jejunum and ileum, and not at all from the colon (Bedford et al 1960;Lin et al 1973;Becker 1984). The fact that all four rats dosed with bipyramidal particles showed an elevated griseofulvin plasma level at 24 h post-dose suggested that the griseofulvin particles were still located in the small intestine at 24 h post-dose and that absorption was continuing.…”

Section: In-vivo Absorption Studiesmentioning

confidence: 97%

Fast-dissolving microparticles fail to show improved oral bioavailability

Wong¹,

Kellaway²,

Murdan³

2006

Journal of Pharmacy and Pharmacology

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Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released approximately 70% of drug compared with approximately 10% from the starting material (particle size 12.61 +/- 1.11 microm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case.

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“…Pharmacological processes that occur in experimental animals after being given griseofulvin: Griseofulvin is absorbed in the duodenum and jejunum, is evenly distributed in most tissues, at some concentrations occurs in the lungs after intravenous dosing 9 . The presence of blood samples from rabbits and mice showed griseofulvin at 65% in plasma, and the remainder in cells 10 . This drug is metabolized in the liver and excreted in the urine.…”

Section: Preclinical Development Pharmacologymentioning

confidence: 98%

“…Intra-molecular Claisen-type reactions (4) and aldol condensation of the heptaketide backbone (5) 47 , respectively yield (6) although neither thioesterase nor cyclase is part of GsfA 44 . GsfB deletion established that griseophenone B (10) accumulates in the GsfF knockout strain. Oxidation of the phenol ring in spirocyclic grisan compounds by phenolic coupling is catalyzed by cytochrome P450 GsfF, in addition the mechanism can be through radical coupling or through arene oxide intermediates.…”

Section: Griseofulvin Biosynthesismentioning

confidence: 99%

Drug Discovery of Griseofulvin : A Review

Jumiati¹,

Chandra²,

Asra³

2021

Asian J Pharm Res Dev

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Background: Griseofulvin is a fungistatic antifungal drug used to treat dermatophytosis. Dermatophytes that are often found include Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum. Purpose: This review article aims to discuss the drug discovery review of griseofulvin. Data Source: The author created this review article using the literature study method relevant to the purpose of the review. Sources of information from national journals and international journals that are accessed through online sites such as Google Scholar, Research Gate, Science Direct, Springer Link, and NCBI. Key words were used to find the journals, namely griseofulvin, dermatophyte, toxicity. Conclusion: The conclusion of this article is that griseofulvin is used as an antifungal drug containing chlorine from Penicillium griseofulvum isolated against mycelium fungus. This drug is non-toxic, so it is effective and safe to fight various types of fungal infections of the skin such as tinea capitis and remains the drug of choice for dermatophytes.

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Studies on the Biological Disposition of Griseofulvin, an Oral Antifungal Agent

Cited by 56 publications

References 3 publications

Studies on the Coumarin Anticoagulant Drugs : A Comparison of the Pharmacodynamics of Dicumarol and Warfarin in Man

Studies on the Coumarin Anticoagulant Drugs : A Comparison of the Pharmacodynamics of Dicumarol and Warfarin in Man

Fast-dissolving microparticles fail to show improved oral bioavailability

Drug Discovery of Griseofulvin : A Review

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