ABSTRACT
The influence of surfactants on the changes in skin barrier properties was investigated in rats. Various ionic and non-ionic surfactants were assessed using indomethacin as a model penetrant. The surfactants appeared to either increase or decrease the skin permeability, due to the properties of both compound and surfactant. Ionic surfactant sodium dodecylsulfate was the most powerful and exceeded controls by approximately 10 times measured by means of serum levels of indomethacin. Other surfactants caused concentration increase or decrease of indomethacin in serum.
Subject(s)
Detergents/pharmacology , Skin Absorption/drug effects , Administration, Cutaneous , Animals , Detergents/administration & dosage , Gels , Indomethacin/administration & dosage , Indomethacin/blood , Indomethacin/pharmacokinetics , Male , Rats , Rats, Inbred StrainsABSTRACT
The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti-inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Azepines/pharmacology , Skin Absorption/drug effects , Terpenes/pharmacology , Administration, Topical , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Azepines/chemistry , Chemical Phenomena , Chemistry, Physical , Cyclohexenes , Limonene , Male , Rats , Rats, Inbred Strains , Solubility , Terpenes/chemistrySubject(s)
Cattle Diseases/prevention & control , Ergolines/pharmacology , Ergolines/therapeutic use , Hypersensitivity, Delayed , Lisuride/pharmacology , Lisuride/therapeutic use , Metipranolol/pharmacology , Propanolamines/pharmacology , Respiratory Tract Diseases/veterinary , Stress, Physiological/immunology , Animals , Blindness , Cattle , Leukocyte Count , Lisuride/analogs & derivatives , Mice , Organ Size/drug effects , Respiratory Tract Diseases/prevention & control , Spleen/drug effects , Thymus Gland/drug effects , VibrationABSTRACT
The lipid mobilizing effects of corticotropin (ACTH), beta 1-24-corticotropin-tetracosactide (TCA) and isoprenaline (ISO) were studied in parallel experiments in older rabbits (six months, weight 3.5 kg) and rats (age 75-85 days, weight 275 g) in vitro. The results were analysed quantitatively. Compared with the effect in younger rats the lipid mobilizing action of ISO in older animals does not differ. The same applies to the very low ISO lipolytic potency in rabbits. The ACTH intrinsic activity and affinity decrease in aging rabbits, but not in aging rats. At the concentration 1 x 10(-9) mol/l of TCA 35% of its maximum effect is reached in rabbits and almost the maximum in rats. In comparison with the maximum response to ACTH the maximum of TCA is two times higher in rabbits whereas in rats it reaches only 80% of the ACTH maximum. The order of the intrinsic activities is in older rats and rabbits different: ISO much greater than ACTH greater than TCA (1.00:0.81:0.64) in rats and TCA greater than ACTH greater than ISO (1.00:0.53:0.31) in rabbits. The affinity relations TCA greater than ISO greater than ACTH are identical in both species with the ratios of ACTH:ISO:TCA = 1:50:1740 in rats and 1:34:915 in rabbits. TCA exerts the strongest lipolytic potency in rats which is 5.5 times greater than in rabbits. On the contrary the intrinsic activity of TCA in rabbits is the highest. In older rabbits the ACTH adipokinetic intrinsic activity and affinity decrease faster than those in ISO. The species differences especially in relation to ISO also remain preserved in older animals and this applies to the TCA lipolytic effects, which in turn do not seem to change with aging as much as the effects of ACTH. When evaluating the species differences or the sensitivity changes connected with aging in the action of lipolytic drugs, the intrinsic activity and affinity should be considered separately.
