Biomaterial Database

Dermatopharmacokinetics of salicylate following topical injection in rats: effect of osmotic pressure and injection volume on salicylate disposition. 2007

Daisuke Yoshida, and Hiroaki Todo, and Tetsuya Hasegawa, and Kenji Sugibayashi

Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.

Using advanced topical formulations containing potential chemical enhancer(s) or physical penetration-enhancing tools capable of delivering entrapped drug(s) directly into skin tissues with little influence of the stratum corneum barrier, local and systemic drug disposition may be markedly similar to direct injection into the skin and muscle. The objective of this study is to investigate the dermatopharmacokinetics and systemic drug disposition after topical application and topical injection. Salicylate (SA) disposition in the skin and muscle as administration sites, and in the systemic circulation were evaluated following intracutaneous (i.c.) injection of an isotonic solution of SA-Na (dose; 3.08 micromol). Subcutaneous (s.c.) and intramuscular (i.m.) injection were also evaluated for comparison. Dermatopharmacokinetics and systemic disposition of SA after i.c. and s.c. injections were analyzed using a 4-compartment model consisting of skin, muscle, and central and peripheral compartments, whereas SA disposition after i.m. injection was analyzed using a 3-compartment model consisting of muscle, and central and peripheral compartments. Moreover, the absorption rate constant of SA after i.c. injection (0.073 min(-1)) was slightly lower than that after s.c. injection (0.083 min(-1)), and much lower than that after i.m. injection (0.327 min(-1)). In addition, higher osmolarity and a larger volume of SA-Na injectant increased the retention of SA in the skin and decreased the absorption rate to the systemic circulation after i.c. injection. The effect of injection volume on SA disposition after i.c. injection was not so marked compared with that of osmotic pressure. These results are useful to design an injection-type topical delivery system.

UI	MeSH Term	Description	Entries
D007271	Injections, Intradermal	The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.	Intradermal Injections,Injection, Intradermal,Intradermal Injection
D007273	Injections, Intramuscular	Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it.	Intramuscular Injections,Injection, Intramuscular,Intramuscular Injection
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D007552	Isotonic Solutions	Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. (From Grant & Hackh's Chemical Dictionary, 5th ed & Dorland, 28th ed)	Solutions, Isotonic
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009997	Osmotic Pressure	The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution.	Osmotic Shock,Hypertonic Shock,Hypertonic Stress,Hypotonic Shock,Hypotonic Stress,Osmotic Stress,Hypertonic Shocks,Hypertonic Stresses,Hypotonic Shocks,Hypotonic Stresses,Osmotic Pressures,Osmotic Shocks,Osmotic Stresses,Pressure, Osmotic,Pressures, Osmotic,Shock, Hypertonic,Shock, Hypotonic,Shock, Osmotic,Shocks, Hypertonic,Shocks, Hypotonic,Shocks, Osmotic,Stress, Hypertonic,Stress, Hypotonic,Stress, Osmotic,Stresses, Hypertonic,Stresses, Hypotonic,Stresses, Osmotic
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