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Organotypic cornea equivalents are used as in vitro models for permeation studies. Many ophthalmic drugs are applied as ester prodrugs to achieve a higher bioavailability. The esterase activity of three corneal human cell lines (epithelial, stromal, endothelial cells) as well as of excised porcine cornea, human donor cornea and human cornea construct (HCC) was investigated and compared. Esterase activity was determined using p-nitrophenyl acetate and hydrocortisone acetate (HCA) as esterase substrates. Hydrocortisone acetate permeation across porcine cornea, human donor cornea and HCC was studied in vitro using Franz-diffusion cells. Corneal epithelial cells showed the highest esterase activity and only small differences to keratocytes and endothelial cells were detectable. The permeation barrier properties of the different corneal tissues were very similar in the case of HCA permeation whereas HCA metabolism rates were in the ranking order of porcine cornea > HCC > human donor cornea. Permeation and metabolism studies indicate that the in vitro permeation model HCC is able to adequately convert hydrocortisone acetate to hydrocortisone.

Background: Topical corticosteroids are the treatment of choice for numerous inflammatory or hyperproliferative skin diseases. The vasoconstriction assay is suitable to determinate corticosteroid activity., Patients and Methods: 60 healthy volunteers were studied. Three corticosteroids in both cream and ointment bases, as well as one corresponding vehicle, were investigated in a double-blind, randomised, intra-individual clinical study, using a vasoconstriction assay. The potencies of hydrocortisone, hydrocortisone-17-butyrate and mometasone furoate were measured, while hydrocortisone-17-butyrate was also compared to the vehicle., Results: The sum score of the clinical evaluation was for Hydrocortisone 34 (cream) and 18 (ointment), for Hydrocortisone butyrate 47 (cream) and 55 (ointment) and for Mometasone furoate 57 (cream) and 50 (ointment). The chromametric values for blanching with hydrocortisone were 1.73 (cream) and 1.48 (ointment), hydrocortisone butyrate 2.87 (cream) and 3.26 (ointment) and mometasone furoate 2.98 (cream) and 2.84 (ointment)., Conclusions: The clinical and chromametric evaluation of vasoconstriction showed activity for all corticosteroid formulations. Hydrocortisone butyrate was shown to be superior to hydrocortisone.

20 patients with highly dosed irradiation of the small pelvis had been treated with Colifoam (hydrocortisone) in order to prove the therapeutic effect of radiation-induced proctitis. Over a period of three to six weeks starting in the third week of irradiation all patients received one applicator filling of rectal foam after bowel movement daily. The findings were verified by proctoscopy, histology and subjective personal well being. In ten patients we determined the daily cortisol profiles. Six months post irradiation ten patients underwent barium enema of the colon. During therapy no major complaints were recorded. The proctoscopic findings showed little changes concerning the submucous vascular walls. In none of the patients any kind of late lesion could be observed. The daily cortisol profile did not show any aberration of the physiological patterns. In conclusion the local therapy of Colifoam can be considered an additional treatment of radiation-induced colitis (proctitis).

Effect of Hydrocortisone Aceponate on Proliferation, Total Protein Synthesis and Collagen Synthesis in Human skin Fibroblasts in vitro. Hydrocortisone aceponate, a new topical hydrocortisone derivative with esterification in positions 17 and 21, inhibits the incorporation of 3H-thymidine in DNA in human skin fibroblasts less strongly than the halogenated glucocorticosteroids betamethasone-17-valerate and clobetasol-17-propionate. Prednicarbate, a prednisolone derivative esterified in positions 17 and 21, possesses antiproliferative properties which are stronger than those of hydrocortisone aceponate, but weaker than those of the halogenated corticosteroids. The glucocorticosteroid effect on total protein and collagen synthesis of skin fibroblasts was determined by measurement of amino acid incorporation. In logarithmically growing cultures, the total protein synthesis rate was stimulated by low corticosteroid concentrations and inhibited by high concentrations. The strongest inhibition was obtained with halogenated glucocorticosteroids. In confluent, non-proliferative cell cultures, all glucocorticosteroids had a stimulating effect on total protein and collagen synthesis. Hydrocortisone aceponate and prednicarbate had a more favourable effect on collagen synthesis than the two halogenated glucocorticosteroid derivatives. According to these results, halogenation and the insertion of double bonds in the steroidal skeleton lead more readily to anti-proliferative effects than esterification in positions 17 and 21.

Even minor adhesions in the oviduct or in the ovarial region may lead to infertility. In a controlled trial the adhesion status was documented in 103 patients who underwent microsurgical operations for infertility. Solutions of (a) streptokinase/streptodornase, (b) hydrocortisone acetate or (c) Ringer's solution only were administered intraperitoneally as adhesion prophylaxis. During a control laparoscopy 1 week after the primary operation, newly formed adhesions of mainly intermediate extent were observed in about 10% of the patients. There was no significant difference in efficacy between the prophylactic treatment.

The paper describes a method for simultaneous thin-layer chromatographic separation of hydrocortisone, hydrocortisone acetate or hydrocortisone caproate alongside dibucaine hydrochloride, hexachlorophene and clemizole undecylate as well as clemizole hexachlorophenate in ointments and suppositories. Development of thin-layer chromatograms is carried out on silica gel 60 F-254 pre-coated plates. All four active ingredients can be separated on one silica gel plate using one solvent system and determined directly by the remission method using a densitometer. Hydrocortisone and its two esters are measured at 248 nm, dibucaine hydrochloride at 325 nm, hexachlorophene at 300 nm, and clemizole undecylate as well as clemizole hexachlorophenate at 275 nm. Evaluation of thin-layer chromatograms takes place on-line from a linear calibration curve using an IBM 1800 computer. The described method is very suitable for analyses of these active ingredients in drug forms, such as ointments or suppositories and is reproducible with coefficients of variation of 1.29-3.56%.

The effect of probenecid on the pharmacokinetics of phenprocoumon (PPC) given as a single oral or intravenous dose, on the vitamin-K-dependent protein-C-antigen, and on the pharmacokinetics of antipyrine and 6 beta-hydroxycortisol was determined in 14 healthy volunteers. Probenecid caused a 75% decrease in urinary excretion of PPC and PPC-glucuronide and shortened the plasma half-life of PPC significantly (by about 35%). The results after oral and intravenous administration of PPC did not differ significantly. Plasma protein-C-antigen concentrations following intravenous PPC were significantly increased by probenecid. The plasma half-life of antipyrine after 7 days of probenecid therapy was significantly diminished. Accordingly, urinary excretion of 6 beta-hydroxycortisol was significantly increased. These data appear for the first time to reveal enzyme-inducing properties of probenecid, which may be responsible for the shortening of PPC plasma half-life when probenecid is given simultaneously. In addition, the influence of probenecid on plasma protein-C-antigen concentrations may indicate further effects of probenecid on liver metabolism.

Tar distillates and topical corticosteroids are still being used to treat chronic eczema. With the use of halogenised corticosteroids local and systemic side-effects are increasing. There fore this both doctor and patient often reject treatment. To avoid this a local treatment with corticosteroids should be effective without having side-effects. In a double-blind investigation we compared a new preparation of 1% hydrocortisone plus 10% urea with hydrocortisone 17-valerate in the treatment of atopic dermatitis. There was no difference between the two preparations concerning the improvement of symptoms and the course of the disease. However, as opposed to the monopreparation, the combination of hydrocortisone and urea caused no side-effects.

In a double-blind controlled study with 27 indoor patients good results were achieved in the treatment of infected dermatoses by fusidic acid and by the combination of fusidic acid with hydrocortisone-17-butyrate.

Within a six-month period, two type-I diabetics were admitted because of labile metabolic state with recurrent severe hypoglycaemia and unconsciousness. In both patients electrolytes were normal on admission. There were at first only few pointers to Addison's disease. But in both primary adrenocortical insufficiency was demonstrated to be the cause of the symptoms. Serological tests suggested an autoimmune genesis. Recurrent severe hypoglycaemia and unconsciousness in insulin-treated diabetics indicates that adrenocortical insufficiency should be excluded.