Difference in percutaneous absorption and intracutaneous distribution in guinea pigs among topical antifungal drugs (tioconazole solution, tioconazole cream, miconazole nitrate solution and bifonazole solution). 2004

Satoshi Sobue, and Kaneo Sekiguchi
Department of Clinical Pharmacology, Pfizer Global R & D, Tokyo Laboratories, Pfizer Japan Inc., Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan. satoshi.sobue@japan.pfizer.com

Tioconazole (TCZ) is an imidazole antifungal agent with broad spectrum activity. Percutaneous absorption and intracutaneous distribution of TCZ solution have been compared with TCZ cream, miconazole nitrate (MCZ) solution and bifonazole (BFZ) solution following a single topical application to abdominal skin of guinea pigs. Following application of TCZ solution, TCZ concentrations in the stratum corneum, epidermis-cutis and subcutaneous tissue were higher than those after TCZ cream application suggesting superior percutaneous penetration after TCZ solution application. The percutaneous penetration after applications of MCZ solution and BFZ solution was comparable to that of TCZ cream, but inferior to that of TCZ solution. TCZ concentrations in the stratum corneum were much higher than those in epidermis-cutis and subcutaneous tissue after applications of both TCZ formulations. The majority of applied TCZ remained in the stratum corneum at high levels for a long duration. TCZ concentrations in the stratum corneum within 24 h after applications of both TCZ formulations were more than several hundred times higher than the minimum inhibitory concentrations against most of the dermatophytes and yeasts. The effectiveness of both TCZ formulations against dermatophytoses may be due to this favorable pharmacokinetic property in the skin tissues, together with its potent antifungal activity. Percutaneous absorption of TCZ after applications of both formulations was negligible suggesting that these treatments are unlikely to produce systemic side effects.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008825 Miconazole An imidazole antifungal agent that is used topically and by intravenous infusion. Brentan,Dactarin,Miconasil Nitrate,Miconazole Nitrate,Monistat,R-14,889,Nitrate, Miconasil,Nitrate, Miconazole,R 14,889,R14,889
D004304 Dosage Forms Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. Dosage Form,Form, Dosage,Forms, Dosage
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000279 Administration, Cutaneous The application of suitable drug dosage forms to the skin for either local or systemic effects. Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area

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