Biomaterial Database

Absorption and metabolism of hydrocortisone 21-butyrate, 21-hemisuccinate and hydrocortisone by skin of the rabbit ear during single-pass perfusion. 1994

G E Bast, and H G Kampffmeyer

Walther-Straub-Institute for Pharmacology und Toxicology, Faculty of Medicine Ludwig-Maximilians-University, Munich, Germany.

1. Rabbit ear was single-pass perfused with protein-free buffer solution at a rate of 0.02 ml/min per cm2 surface area for up to 6 h. 2. Hydrocortisone or hydrocortisone 21-butyrate or hydrocortisone 21-hemisuccinate was applied dermally (0.01-1.0% w/w) in suspension with isopropyl myristate or dissolved in 1,2-propanediol. The ointments were stiffened with 5% polyethylene 1500 or 1.2% methylcellulose respectively. 3. Hydrocortisone was slowly absorbed and did not reach a steady-state absorption rate during the experimental period. 4. No metabolites of hydrocortisone were found during ear perfusion. In the supernatant of skin homogenate, however, cortisone, hydrocortisone-20 alpha-ol and another, as yet unidentified metabolite, were observed. 5. Hydrocortisone 21-butyrate was completely hydrolysed during dermal absorption, showing steady-state concentrations of hydrocortisone in the effluent. Hydrocortisone 21-hemisuccinate did not reach steady-state concentrations in the effluent. About two-thirds was hydrolysed during absorption. 6. During arterial perfusion approximately 30% of hydrocortisone 21-butyrate was hydrolysed whereas 97% of hydrocortisone 21-hemisuccinate remained intact. 7. First-pass ester hydrolysis in skin may be complete for the poorly absorbed glucocorticoids leading to metabolites of less lipophilicity.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009226	Myristates	Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid.	Tetradecanoates
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D011409	Propylene Glycols	Derivatives of propylene glycol (1,2-propanediol). They are used as humectants and solvents in pharmaceutical preparations.	Propanediols,Glycols, Propylene
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D004423	Ear	The hearing and equilibrium system of the body. It consists of three parts: the EXTERNAL EAR, the MIDDLE EAR, and the INNER EAR. Sound waves are transmitted through this organ where vibration is transduced to nerve signals that pass through the ACOUSTIC NERVE to the CENTRAL NERVOUS SYSTEM. The inner ear also contains the vestibular organ that maintains equilibrium by transducing signals to the VESTIBULAR NERVE.	Vestibulocochlear System,Vestibulocochlear Apparatus,Apparatus, Vestibulocochlear,Ears,System, Vestibulocochlear
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000042	Absorption	The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
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