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At least 19 recordsLinked to original sources
PubMed1995

Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo.

It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.

Administration, Topical↗
PubMed1981

Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [3H]hydrocortisone.

After administration of [3H]hydrocortisone to adrenalectomized rats, hormone-protein complexes were isolated from liver cytosol by DEAE-cellulose chromatography. After application of biologically active and inactive doses of hydrocortisone five binding components were detected eluting at the same salt concentrations as the hormone-protein complexes observed after incubation of cytosol with [3H]hydrocortisone in vitro. The isolated hormone-protein fractions were acidified and extracted with ethylacetate and the steroids were analyzed by thin-layer chromatography. No significant amount of hydrocortisone could be detected in any of the complexes formed in vivo 5-60 min after administration of biologically active doses of hydrocortisone. 3 xi, 11 beta, 17 alpha, 20 xi, 21-Pentahydroxypregnane, steroidal carboxy acids, glucuronides and a very polar conjugate of hydrocortisone were found in the different fractions. After an in vivo dose of hydrocortisone of about 1/5000th of the minimal dose required for enzyme induction, hydrocortisone could be found in all the cytoplasmic hormone-protein complexes formed. In contrast to the cytoplasmic hormone-protein complexes, hydrocortisone could be readily demonstrated in nuclei isolated after the administration of biologically active doses of hormone, although acid metabolites were found to represent the main part of the radioactive compounds present in the nuclei. These acid metabolites were located in the nuclear envelope. These results seem to contradict the generally accepted theory that hydrocortisone induces biosynthesis of proteins via a cytoplasmic hydrocortisone-receptor complex: after administration of biologically active doses of hydrocortisone, no such complex could be detected.

Adrenalectomy↗
PubMed1994

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

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.

Absorption↗
PubMed1982

Effect of dose size on the pharmacokinetics of intravenous hydrocortisone during endogenous hydrocortisone suppression.

The pharmacokinetics of hydrocortisone were examined following single intravenous doses of 5, 10, 20, and 40 mg hydrocortisone, as the sodium succinate salt, to healthy male volunteers. Endogenous hydrocortisone was suppressed by administration of 2 mg dexamethasone the night before hydrocortisone injection. Plasma samples obtained serially during 8 h after hydrocortisone injection were assayed by reverse-phase HPLC using a fixed wavelength (254 nm) ultraviolet detector. Initial concentrations of hydrocortisone in plasma were proportional to dose size. The subsequent decline in hydrocortisone concentrations was biphasic, and individual data sets were adequately described in terms of the pharmacokinetic two-compartment open model. Values of pharmacokinetic parameters were similar from the 5, 10, and 20 mg doses. Following the 40 mg dose, the overall elimination rate constant decreased, while the distribution volume, Vdss, and plasma clearance increased, in comparison with the values obtained from lower doses. Changes in the pharmacokinetics of hydrocortisone at high doses may be related to drug concentration-dependent changes in the binding of hydrocortisone to plasma proteins. Previously reported dose-dependent changes in some pharmacokinetic parameters following oral hydrocortisone are attributed to absorption rather than distribution or elimination effects.

Adult↗
PubMed1986

Sensitivity to hydrocortisone is a relevant factor in the immunoendocrine relationship. I. The cell-mediated immune response in relation to blood levels and in vitro immunosuppressive effects of hydrocortisone in patients with asthma and healthy control subjects.

The role of endogenous hydrocortisone in the regulation of lymphocyte activity was assayed in patients with asthma (patients with chronic nonspecific lung disease, characterized by attacks of dyspnea, alternating with symptom-free periods) and healthy control subjects. After priming, delayed-type hypersensitivity skin reactions were induced with Helix pomatia hemocyanin (HPH). Hydrocortisone blood levels were measured. The effect of hydrocortisone on HPH-induced lymphocyte proliferation was determined in vitro. The results demonstrate that hydrocortisone in low concentrations (100 ng/ml) inhibited in vitro lymphocyte proliferation equally in patients and control subjects. However, both groups demonstrated a large interindividual variation in hydrocortisone sensitivity. Therefore, in order to determine the immunologic effect of hydrocortisone blood levels in vivo, a hydrocortisone suppression index (HSI) was calculated by use of the information on hydrocortisone concentrations in vivo and the biologic effect of hydrocortisone in vitro. This HSI appeared to be inversely related with the in vivo cell-mediated immune response to HPH. This was reflected in an inverse correlation between HSI and delayed-type hypersensitivity skin reactions to HPH, both in patients (R = -0.64), in control subjects (R = -0.69), and in the total group (R = -0.68; p less than 0.001). No differences were observed between patients and control subjects. It is concluded that endogenous hydrocortisone is likely to play an important role in the regulation of lymphocyte activity in patients with asthma and healthy control subjects. This may have important consequences for the clinical expression of asthmatic symptoms, since the role of lymphocyte activity in the pathogenesis of asthma is increasingly recognized.

Adult↗
PubMed1952

Rheumatoid arthritis; experiences with hydrocortisone (free alcohol) and hydrocortisone acetate.

Recent experimental evidence suggests that hydrocortisone (Kendall's Compound F) is probably the principal glycogenic steroid secreted by the adrenal cortex and that under conditions of stress it may participate more than cortisone in physiologic reactions. Laboratory studies indicate that hydrocortisone has greater physiologic activity, milligram for milligram, than cortisone and with certain assays its potency is twice as great.Two forms of hydrocortisone, the free alcohol preparation and the acetate, were given systemically to patients with rheumatoid arthritis and were observed to possess significant differences in ability to suppress the disease manifestations. When administered orally in large initial doses, hydrocortisone (free alcohol) appeared to produce greater suppressive effects, milligram for milligram, than either hydrocortisone acetate or cortisone acetate. Comparisons of potency made by determining maintenance dosage requirements for equivalent degrees of clinical control in the same patients indicated that the effectiveness of hydrocortisone (free alcohol) is more than 50 per cent greater than that of either the free or acetated forms of cortisone and approximately twice as great as that of hydrocortisone acetate. Certain observations suggested that the greater antirheumatic activity of hydrocortisone (free alcohol) is not accompanied by a correspondingly greater tendency toward endocrine complications. If more extensive future investigations support this observation, hydrocortisone (free alcohol), by producing equally efficient results with smaller doses, may prove superior to cortisone as a therapeutic agent.Intra-articular injections of hydrocortisone acetate appear to have only a limited place in the management of rheumatoid arthritis but may be used for temporary relief under certain conditions. In preliminary studies by the author it was noted that whereas improvement resulted in 80 per cent of the treated joints, the improvement was graded as pronounced or very pronounced in only one-half of the joints so injected. In almost all instances the benefits derived were quite temporary. Results observed in treatment of osteoarthritic joints by this method were decidedly poorer than in rheumatoid arthritis.

Adrenal Cortex↗
PubMed1976

Enzyme inhibition in human skin homogenates by hydrocortisone, hydrocortisone acetate and hydrotisone butyrate.

In fresh human skin homogenates, the activities of four enzymes, lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), "acid" phosphatase (AcP), and "leucine aminopeptidase" (LAP) were assayed following an incubation with hydrocortisone, hydrocotisone acetate, or hydrocortisone-17-butyrate, respectively. Concentration of the three compounds measured 2.75 mMol/l. Hydrocortison butyrate inhibited LDH-G-6-PDH-, and AcP-activities. Hydrocortisone and hydrocortisone acetate exerted a significant inhibitory action only in the case of G-6-PDH-activity.--On pure G-6-PDH from yeast, the inhibition exerted by hydrocortisone butyrate was significantly stronger than the inhibition exerted by the two other steroids. Time/action diagrams revealed the fact that hydrocortisone butyrate is superior to the other two compounds from the beginning of the incubation period.--The date sustain the assumption that hydrocortisone butyrate exerts biochemical-pharmacological actions of its own and that it may not be considered just as an esterified transport form of hydrocortisone.

Acetates↗
PubMed2005

[Comparison of activity of different topical corticosteroid creams and ointments using a vasoconstriction assay: superiority of hydrocortisone butyrate over 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.

Administration, Topical↗
PubMed1982

Oral hydrocortisone pharmacokinetics: a comparison of fluorescence and ultraviolet high-pressure liquid chromatographic assays for hydrocortisone in plasma.

Three fasted, male subjects received single 10-, 30-, and 50-mg oral doses of hydrocortisone tablets on separate occasions. Endogenous hydrocortisone was suppressed by giving 2 mg of dexamethasone 9 hr prior to dosing. Plasma samples obtained serially for 8 hr after hydrocortisone dosing were assayed by reversed-phase high-pressure liquid chromatography (HPLC) with UV detection and by normal-phase HPLC with fluorescence detection of the dansylhydrazine derivative of hydrocortisone. The two assay methods yielded equivalent plasma hydrocortisone concentrations. Metabolite interference was absent in both assay methods. Drug concentrations in plasma from all three doses of hydrocortisone were described by one-compartment open-model kinetics, with first-order absorption and elimination, and an absorption lag time. Mean Cmax values of 199, 393, and 419 ng/ml were obtained at 1.0, 1.0, and 1.7 hr following the 10-, 30-, and 50-mg doses, respectively. Hydrocortisone was cleared from plasma with an elimination half-life of approximately 1.5 hr. Within the dosage range studied, plasma levels of hydrocortisone were related, but not directly proportional, to dose size. This apparent lack of proportionality may be due to reduced drug availability or altered distribution with increasing dose.

Administration, Oral↗
PubMed1991

Screening for corticosteroid contact sensitivity. Comparison of tixocortol pivalate, hydrocortisone-17-butyrate and hydrocortisone.

3 corticosteroids have so far been tried as markers for corticosteroid contact sensitivity: hydrocortisone, tixocortol pivalate and hydrocortisone-17-butyrate. The present study compared these steroids for screening in addition to a standard patch test series. Of 727 patients, 28 (3.9%) reacted to tixocortol pivalate and 10 (1.4%) to hydrocortisone-17-butyrate; hydrocortisone gave an allergic reaction in 2 of 521 (0.4%) patients. Serial dilutions suggested that tixocortol pivalate, not marketed in Finland, caused allergic reactions which could possibly be cross-reactions to hydrocortisone. In contrast to previously published data, frequent cross-reactions occurred with hydrocortisone-17-butyrate and tixocortol pivalate. All allergic reactions to other corticosteroids found by testing with tixocortol pivalate concurred with reactions to hydrocortisone-17-butyrate. The study suggests that the most effective choice for routine testing for corticosteroid contact sensitivity would be both tixocortol pivalate and hydrocortisone-17-butyrate.

Administration, Topical↗
PubMed1980

Study of the effects of hydrocortisone and hydrocortisone 17-butyrate ointments on plasma ACTH levels and Synacthen responses in children with eczema.

This study compares the effects on the hypothalamo-pituitary adrenal (HPA) axis of two dosage schedules of hydrocortisone 17-butyrate and hydrocortisone ointments in 20 children suffering from eczema. Children with moderately extensive eczema received either 30 g of 0.1% hydrocortisone 17-butyrate or 30 g of 1% hydrocortisone ointment weekly for 4 weeks without occlusion. Children with extensive eczema received either 60 g of hydrocortisone 17-butyrate or 60 g of hydrocortisone weekly for 4 weeks. All four groups showed some clinical improvement. Although many of the children appeared to have some impairment of adrenal function prior to entering the trial, no further significant depression of the HPA axis as reflected by the plasma ACTH levels and a 30-min Synacthen test was observed during the trial. On the basis of 4 weeks' treatment, hydrocortisone 17-butyrate did not have a significantly different effect on the HPA axis in children from that of hydrocortisone.

Administration, Topical↗
PubMed1992

Inhibition by epidermal growth factor (EGF) of epidermal DNA synthesis in cultured chick embryonic skin pretreated with retinol and/or hydrocortisone: specific increment in EGF binding activity in both retinol- and hydrocortisone-pretreated epidermis without correlation to EGF-mediated inhibition of cell growth.

When tarsometatarsal skin of 13-day-old chick embryos that had been cultured in medium containing 5% delipidized FCS with or without retinol (20 microM) and/or hydrocortisone (20 nM) for 1 day was cultured in a chemically defined medium without either the hormone or retinol for 1 day, epidermal DNA synthesis of hydrocortisone- and/or retinol-pretreated skin was inhibited when compared to that of control skin. The addition of epidermal growth factor (EGF, 10 ng/ml) to retinol- or hydrocortisone-pretreated skin further inhibited the epidermal DNA synthesis. Epidermal DNA synthesis in retinol- and hydrocortisone-pretreated skin was more strongly inhibited than in retinol- or hydrocortisone-pretreated skin, but was not further inhibited by EGF. In epidermis which was induced to differentiation toward keratinization by hydrocortisone or mucous metaplasia by retinol, EGF inhibited DNA synthesis. The extent of [125I]-EGF binding to the epidermis of retinol- and hydrocortisone-pretreated skin was 160-180% that in control skin, with no change in affinity. Hence there is no correlation between EGF-binding and the mitogenic activity of EGF.

Animals↗
PubMed1986

Seborrhoeic dermatitis and Pityrosporum orbiculare: treatment of seborrhoeic dermatitis of the scalp with miconazole-hydrocortisone (Daktacort), miconazole and hydrocortisone.

Seventy patients (36 males and 34 females) with seborrhoeic dermatitis of the scalp were treated in a double-blind controlled study, for a maximum of 6 weeks, with 2% miconazole base and 1% hydrocortisone (Daktacort), 2% miconazole base, or 1% hydrocortisone. Patients who were cured were treated with the same formulation prophylactically twice monthly for 3 months or until recurrence. Nineteen of 21 patients were cured in the Daktacort group, 15 of 22 in the miconazole group and 17 of 24 in the hydrocortisone group. The number of cultured Pityrosporum orbiculare was significantly lower in all groups after treatment, but in the hydrocortisone group was still significantly higher than in the two other groups. After 3 months of prophylactic treatment, both Daktacort (16 of 19 patients clear) and miconazole (10 of 15 patients clear) were significantly better than hydrocortisone (3 of 17 patients clear) (P less than 0.01). The numbers of P. orbiculare remained low in the Daktacort and miconazole groups and also significantly lower than in the hydrocortisone-treated group (P less than 0.01). In patients with recurrence, the numbers returned to pre-treatment levels. This study demonstrates the aetiological significance of the Pityrosporum yeasts in seborrhoeic dermatitis. Both Daktacort and miconazole were effective in treatment and as prophylactic agents.

Adult↗
PubMed1987

Hydrocortisone succinate and hydrocortisone simultaneously determined in plasma by reversed-phase liquid chromatography, and their pharmacokinetics in asthmatic children.

Hydrocortisone succinate and hydrocortisone are chromatographed with a mobile phase consisting of sodium acetate/acetonitrile (77/23, by vol), the effluent being monitored at 254 nm. p-Hydroxybenzoate-N-propyl is used as the internal standard. Detection limits are 0.5 mg/L for hydrocortisone succinate, 0.2 mg/L for hydrocortisone. For five different concentrations the respective mean analytical recoveries were 88.2% and 100.5%, the mean intra-assay CVs for slope 3.9% and 2.1%, and the inter-assay CVs 3.3% and 1.6%. Simultaneous measurement of hydrocortisone and its succinate ester may be useful for pharmacokinetic study. Concentration-time profiles for plasma after administration of hydrocortisone sodium succinate are presented.

Adolescent↗