Griseofulvin absorption

Gramatte, T., Griseofulvin absorption from different sites in the human small intestine, Biopharm. Drug Dispos. 1994, 15, 747-759. 

Absorption from the gastrointestinal tract can be affected by other drugs and by food. Aluminum, calcium, and magnesium ions in antacids or dairy products form insoluble chelates with all tetracyclines and inhibit their absorption. Food inhibits tetracycline absorption but enhances doxycycline absorption food delays but does not diminish metronidazole absorption fatty food enhances griseofulvin absorption. 

Tetracycline, when given in full stomach, the blood level are reduced by 55 to 80% as compared with fasting individuals. The griseofulvin absorption is enhanced by giving it with fatty meals. 

Shah VP, Riegelman S, Epstein WL. Griseofulvin absorption, metabolism and excretion. In Robinson HM, editor. The Diagnosis and Treatment of Fungal Infections. Sprnigfield IL Thomas, 1974 315. 

Katchen B, Symchowicz S (1967). Correlation of dissolution rate and griseofulvin absorption in man. 

The rate and probably extent of griseofulvin absorption is markedly increased if it is taken with a high-fat meak... 

Griseofulvin is adminisfered orally in the form of tablets. It is not totally absorbed when given orally, and one method of increasing absorption is to reduce the particle size of the drug. Griseofulvin is deposited in the deeper layers of the skin and in hair keratin, and is therefore employed in chemotherapy of fungal infections of these areas caused by susceptible organisms. 

Drugs in Class II have low aqueous solubility (but high membrane permeability), and any factor affecting dissolution rate would be expected to have an impact on the absorption of such compounds. Factors that are noted in Fig. 11, such as fluid pH, volume and viscosity, and bile secretion (especially in response to fatty foods), might be expected to play a role in dissolution rate and thereby affect absorption. Compounds that fall into this class include carbamazepine, cyclosporin, digoxin, griseofulvin, and spironolactone. Food would be expected to exert a potentially significant affect on... 

RG Crounse. Human pharmacology of griseofulvin. The effect of fat intake on gastrointestinal absorption. J Invest Dermatol 37 529-533, 1961. 

M Kraml, J Dubuc, D Beall. Gastrointestinal absorption of griseofulvin. I. Effect of particle size, addition of surfactants and corn oil on the level of griseofulvin in the serum of rats. Can J Biochem Physiol 40 1449-1451, 1962. 

Crison and Amidon [47,48] recently used the mass balance approach to study the variability in absorption due to intestinal transit time for water-insoluble drugs. As expected, for low dose drugs, such as digoxin, the variability in absorption sharply decreases with the increase of dissolution number via micronization. For high dose drugs, such as griseofulvin, little effect was observed when the dissolution number was increased by micronization. 

M Kraml, J Dubuc, R Gaudry. Gastrointestinal absorption of griseofulvin II. Influence of particle size in man. Antibiot Chemother 12 239-242, 1962. 

Jamali F, Axelson JE. Influence of metoclopramide and propantheline on GI absorption of griseofulvin in rats. J Pharm Sci 1977 66 1540-1543. 

There are occasional anomalies to the rule that food reduces and delays peak plasma concentration. The anti-fungal drug, griseofulvin, has enhanced absorption if taken with a meal - possibly because it becomes emulsified by bile salts and passes more readily into the lymphatic drainage of the gut which bypasses the liver, entering the venous system directly. The immuno-suppressant cyclosporin, and calcium salts in general, show a similar increase in absorption when taken with a fatty meal. 

Ineffective topically, griseofulvin is administered orally but has poor gastrointestinal absorption absorp-... 

Take griseofulvin with foods high in fat, such as milk or ice cream, to reduce G1 upset and assist in drug absorption... 

Griseofulvin, a BCS class II drug (Fig. 2), is a well-known example whose poor aqueous solubility causes low and erratic oral bioavailability. As shown below, griseofulvin has a hydrophobic molecular structure, and is practically insoluble in water. Its oral absorption is highly variable, ranging from 25% to 100%, depending on the crystal size. Ultramicrosize griseofulvin preparations were shown to have 100% oral absorption (12). 

For a typical drug with zero-order absorption, the concentrations after oral administration rise to a sharp peak and then quickly decline with no intermediate plateau. Examples of insoluble drugs whose absorption processes follow zero-order kinetics are cyclosporine (Grevel et al., 1986) and griseofulvin (Bates and Carrigan, 1975). 

---