Clinical pharmacokinetics and pharmacodynamics of topical non-biological therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory cutaneous disease that causes patients psychosocial distress. Topical therapies are utilized for mild-to-moderate disease and for more severe disease in conjunction with systemic therapies. Topical corticosteroids are a cornerstone of treatment for psoriasis, but long-term use can cause stria and cutaneous atrophy and as well as systemic side effects such as topical steroid withdrawal. Non-steroidal topical therapies tend to be safer than topical corticosteroids for long-term use. AREAS COVERED: We conducted a literature review on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of topical therapies for psoriasis. We discuss how the PK and PD characteristics of these therapies inform clinicians on efficacy and toxicity when prescribing for patients. EXPERT OPINION: Topical corticosteroids, used intermittently, are very safe and effective. Long-term, continuous use of topical corticosteroids can cause systemic side effects. Several generic and newly approved non-steroidal options are available, but no head-to-head studies compare the effectiveness of the generics (vitamin D analogs, tacrolimus, pimecrolimus) against the newer therapies (roflumilast, tapinarof). Patients often do not respond to topical therapies due to poor adherence to treatment regimens. For patients resistant to topical treatment, phototherapy or systemic therapy may be an option.

Effects of Ice Massage Prior to an Iontophoresis Treatment Using Dexamethasone Sodium Phosphate.

CONTEXT: Low current intensity iontophoresis treatments have increased skin perfusion over 700% from baseline potentially altering drug clearance from or diffusion to the targeted area. OBJECTIVE: To determine the effects of a preceding 10-minute ice massage on subcutaneous dexamethasone sodium phosphate (Dex-P) concentration and skin perfusion during and after a 4-mA iontophoresis treatment. DESIGN: Controlled laboratory study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four participants (male = 12, female = 12; age = 25.6 [4.5] y, height = 173.9 [8.51] cm, mass = 76.11 [16.84] kg). INTERVENTION(S): Participants were randomly assigned into 2 groups: (1) pretreatment 10-minute ice massage and (2) no pretreatment ice massage. Treatment consisted of an 80-mA·minute (4 mA, 20 min) Dex-P iontophoresis treatment. Microdialysis probes (3 mm deep in the forearm) were used to assess Dex-P, dexamethasone (Dex), and its metabolite (Dex-Met) concentrations. Skin perfusion was measured using laser Doppler flowmetry. MAIN OUTCOME MEASURE(S): Microdialysis samples were collected at baseline, at conclusion of treatment, and every 20 minutes posttreatment for 60 minutes. Samples were analyzed to determine Dex-Total (Dex-Total = Dex-P + Dex + Dex-Met). Skin perfusion was calculated as a percentage change from baseline. A mixed-design analysis of variance was used to determine Dex-Total and skin perfusion difference between groups overtime. RESULTS: There was no difference between groups (P = .476), but [Dex-Total] significantly increased over the course of the iontophoresis and posttreatment time (P < .001). Dex-P was measured in 18 of 24 participants with a mean concentration of 0.67 (1.09) µg/mL. Skin perfusion was significantly greater in the no ice treatment group (P = .002). Peak skin perfusion reached 27.74% (47.49%) and 117.39% (103.45%) from baseline for the ice and no ice groups, respectively. CONCLUSIONS: Ice massage prior to iontophoresis does not alter the tissue [Dex-Total] even with less skin perfusion.

Physiologically Based Pharmacokinetics of Dexamethasone in Rats.

Blood and multitissue concentration-time profiles for dexamethasone (DEX), a synthetic corticosteroid, were measured in male rats after subcutaneous bolus and infusion dosing. A physiologically based pharmacokinetics (PBPK) model was applied for 12 measured tissues. Tissue partition coefficients (K p ) and metabolic clearance were assessed from infusion studies. Blood cell to plasma partitioning (0.664) and plasma free fraction (0.175) for DEX were found to be moderate. DEX was extensively partitioned into liver (K p = 6.76), whereas the calculated K p values of most tissues ranged between 0.1 and 1.5. Despite the moderate lipophilicity of DEX (log P = 1.8), adipose exhibited very limited distribution (K p = 0.17). Presumably due to P-glycoprotein-mediated efflux, DEX concentrations were very low in brain compared with its expected high permeability. Infusion studies yielded K p values from male and female rats at steady state that were similar. In silico K p values calculated for different tissues by using GastroPlus software were similar to in vivo values except for adipose and liver. Glucocorticoid receptors are found in diverse tissues, and these PBPK modeling results may help provide exposure profiles driving pharmacodynamic effects of DEX. SIGNIFICANCE STATEMENT: Our physiologically based pharmacokinetics model describes the experimentally determined tissue and plasma dexamethasone (DEX) pharmacokinetics (PK) profiles in rats reasonably well. This model can serve for further investigation of DEX tissue distribution in rats as the PK driving force for PD effects in different tissues. No major sex differences were found for DEX tissue distribution. Knowledge gained in this study may be translatable to higher-order species including humans.

Novel hydrogel-based ocular drug delivery system for the treatment of conjunctivitis.

PURPOSE: Conventional dosage form like eye drops showed poor therapeutic response and also require frequent dosing. Therefore, developing the dosage form to deliver the drug to the target site without much loss of drug or without causing any systemic side effects is the challenging job for the researchers in pharmaceutical industries. OBJECTIVE: The main aim of the present work was to formulate and evaluate hydrogel-based drug delivery containing combination of neomycin sulphate and betamethasone sodium phosphate in order to provide prolonged release and also better bioavailability of drugs for the treatment of eye infections. METHODS: In this study, poloxamer 407 and chitosan at different concentrations were used as the gelling agents. The prepared formulations were evaluated for clarity, pH, drug content, gelling capacity, gelling temperature and in vitro drug release study. RESULTS: From the preliminary studies, F5 formulation was selected as an optimized formulation. The optimized formulation was further evaluated for ex vivo permeation study, sterility test, HET-CAM and ocular irritation testing using rabbits. Ocular irritation by HET-CAM assay showed that the formulated gel does not cause any irritation to the blood vessels. Draize irritation test was performed using rabbits and results showed that formulation was non-irritant to the eye. CONCLUSION: The formulated hydrogel formulation can be used as an alternative to conventional ophthalmic eye drop formulation of drugs neomycin and betamethasone for the purpose of providing prolonged therapy for the treatment of conjunctivitis.

Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends.

Dexamethasone is one of the most prescribed glucocorticoids. It is effective and safe in the treatment of a wide variety of ocular conditions, including anterior and posterior segment inflammation. However, its half-life in the vitreous humor is very short, which means that it typically requires frequent administrations, thus reducing patient adherence and causing therapeutic failure. Innovative dexamethasone delivery systems have been designed in an attempt to achieve sustained release and targeting. The FDA has approved dexamethasone implants for the treatment of macular edema secondary to retinal vein occlusion and posterior segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes, micelles and dendrimers are also proving to be adequate systems for maintaining optimal dexamethasone levels in the site of action. Pharmaceutical technology is turning a classical drug, dexamethasone, into a fashionable medicine.

Budesonide/salmeterol in fixed-dose combination for the treatment of asthma.

Fixed dose combinations (FDC) of inhaled corticosteroid (ICS) and long-acting beta agonist (LABA) are well established in asthma treatment. The budesonide/salmeterol (B/S) FDC is now about to reach the market. It is provided as powder in hard capsules of two strengths: 120/20µg and 240/20µg when expressed as delivered doses, equivalent to 150/25µg and 300/25µg when expressed as nominal doses. Its development involved 9 pharmacokinetic (320 subjects), 3 phase II (123 subjects) and 4 phase III (1206 patients with different asthma severity) studies. Delivery is effectuated via low resistance inhaler device, Axahaler®, generating also fine particles targeting the small airways. B/S safety, assessed in 1401 subjects, did not outline novel concerns specific for this FDC. In conclusion, the B/S dry powder FDC can be used for asthma treatment in adults not adequately controlled on ICS alone, or to maintain control of ICS/LABA treated patients, in whom switching to alternative FDC is indicated.

Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study.

AIM: This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. METHODS: Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS: ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.

[Principles of glucocorticoid therapy]. / Prinzipien der Steroidtherapie.

The principles of systemic glucocorticoid (GC) therapy in dermatology are reviewed. As a basis for an efficient GC therapy with few side effects the pharmacology, endogenous regulation as well as the mechanisms and side effects of GCs as well as their management are introduced. Modern therapeutic approaches such as circadian application and low-dose therapy are discussed as well as principles of tapering dosages and the most important indications for systemic GCs in dermatology.

Progress in study on synergism and detoxification of Chinese medicine for glucocorticoid.

Glucocorticoid (GC) plays an important role in anti-inflammatory, anti-allergic effects and immunosuppression, and has become a widely used drug in clinical departments. However, GC also produces a number of serious side effects at the same time. After GC acting on human body, the syndrome change has some regular pattern and it can be treated on the basis of syndrome differentiation and stage to aim at further improving therapeutic efficacy. The Chinese medicine can reduce the side effects of GC when treating the primary disease, thus plays a role in Synergism and Detoxification.

Pharmacokinetics of triamcinolone acetonide for the treatment of macular edema.

INTRODUCTION: The use of intravitreal triamcinolone acetonide (TA) for the treatment of various types of macular edema has been widespread, particularly for the last decade. Currently, there is a scant amount of evidence-based literature evaluating the pharmacokinetic profile of TA despite clinical data showing the efficacy of intravitreal TA for multiple forms of macular edema. AREAS COVERED: This paper is an extensive review of human and experimental studies published on the pharmacokinetics of TA for the treatment of macular edema. The literature search was conducted via OVID, TRIP Database and EMBASE, up to April 2011. EXPERT OPINION: The pharmacokinetic profile of TA is unpredictable and the agent has a time-limited therapeutic action due to its relatively short half-life. This has led to the need for repeated injections. Future research should investigate the pharmacokinetic profiles of TA when administered intravitreally, as well as through alternate routes in more robust studies.

Development and validation of a fast and sensitive bioanalytical method for the quantitative determination of glucocorticoids--quantitative measurement of dexamethasone in rabbit ocular matrices by liquid chromatography tandem mass spectrometry.

A sensitive, selective, accurate and robust LC-MS/MS method was developed and validated for the quantitative determination of glucocorticoids in rabbit ocular tissues. Samples were processed by a simple liquid-liquid extraction procedure. Chromatographic separation was performed on Phenomenex reversed phase C18 gemini column (50mmx4.6mm i.d.,) with an isocratic mobile phase composed of 30% of acetonitrile in water containing 0.1% of formic acid, at a flow rate 0.2mL/min. Dexamethasone (DEX), prednisolone (PD) and hydrocortisone (HD) were detected with proton adducts at m/z 393.20-->355.30, 361.30-->147.20 and 363.20-->121.0 in multiple reaction monitoring (MRM) positive mode respectively. Finally, 50microL of 0.1% novel DEX mixed micellar formulation was topically administered to a rabbit eye and concentrations were measured. The method was validated over a linear concentration range of 2.7-617.6ng/mL. Lower limit of quantitation (LLOQ) of DEX and PD was measured in the concentration range of 2.7 and 11.0ng/mL respectively. The resulting method demonstrated intra and inter-day precision within 13.3% and 11.1% and accuracy within 19.3% and 12.5% for DEX and PD, respectively. Both analytes were found to be stable throughout freeze-thaw cycles and during bench top and postoperative stability studies (r(2)>0.999). DEX concentrations in various ocular tissue samples i.e., aqueous humor, cornea, iris ciliary body, sclera and retina choroid were found to be 344.0, 1050.07, 529.6, 103.9 and 48.5ng/mg protein respectively. Absorption of DEX after topical administration from a novel aqueous mixed micellar formulation achieved therapeutic concentration levels in posterior segment of the rabbit eye.

Lecithin/chitosan nanoparticles of clobetasol-17-propionate capable of accumulation in pig skin.

In this study, clobetasol-17-propionate (CP) loaded lecithin/chitosan nanoparticles were studied with special attention to the transport of the active agent across the skin in vitro. Nanoparticles were characterized by measuring particle size, zeta potential, polydispersity index and encapsulation efficiency. The morphology of nanoparticles was evaluated by transmission electron microscopy. Encapsulation experiments with CP showed high encapsulation efficiency (92.2%). To assess the advantages of this carrier-based formulation in topical administration, the accumulation in and permeation across pig ear skin were compared with chitosan gel and commercially available cream of CP. The results obtained indicate that the incorporation of drug into nanoparticles induced an accumulation of CP especially in the epidermis without any significant permeation across the skin. Dilution of CP loaded nanoparticles with chitosan gel (1:9) produced the same amount of CP in the skin compared with commercial cream, although the former contained ten times less CP. This is a remarkable point for the reduction of the side effects of CP. These results demonstrated the suitability of lecithin/chitosan nanoparticles to induce epidermal targeting and to improve the risk-benefit ratio for topically applied CP.

Systemic effects of intra-articular corticosteroids.

The objective of this study was to review all the published articles in the English literature about the systemic effects of intra-articular corticosteroid injection (IACI) in humans. Reports were searched through Pubmed using the terms intraarticular or intra-articular and steroids, corticosteroids, or glucocorticosteroids up and including the year 2007. Reports were also located through references of articles. Only objective findings outside the injected joint were included. The overwhelming majority of the studies was done at the knee joint and in rheumatoid arthritis/juvenile idiopathic arthritis patients. Many of the studies were done on the hypothalamic-pituitary-adrenal axis. Serum cortisol decreased within hours with a nadir after usually 24-48 h following the IACI. Recovery to baseline takes 1-4 weeks and sometimes longer depending on the type and dose of IACI and on the number of injected joints. Serum cortisol levels were blunted following adrenocorticotropic hormone stimulation in a small proportion of patients following methylprednisolone acetate injection and more common following other preparations. IACI resulted in a transient increase in blood glucose levels over few days in controlled diabetic patients with knee osteoarthritis. Peak levels are around 300 mg%. IACIs are associated with reduction in inflammatory markers like C-reactive protein and erythrocyte sedimentation rate that start few days following the IACI and could last for months. The effect on inflammatory cytokines is immediate with significant decrease within hours. IACI may induce remission also in patients with oligo-/polyarthritis and/or in patients with extra-articular manifestations. Other metabolic, hematologic, vascular, allergic, visual, psychologic, and other effects were also reported.

The distribution, release kinetics, and biocompatibility of triamcinolone injected and dispersed in silicone oil.

PURPOSE: Triamcinolone acetonide (TA) has been proposed as an adjuvant to pars plana vitrectomy with silicone oil for the surgical treatment of proliferative vitreoretinopathy and proliferative diabetic retinopathy. However, to date no data about the distribution and pharmacokinetics of lipophilic TA injected into silicone oil have been reported. METHODS: An artificial vitreous space chamber was filled with silicone oil. TA was either injected or dispersed into silicone oil. TA release using a continuous flow model was measured spectrophotometrically. To determine the antiproliferative or cytotoxic effect of the released TA, monolayer cultures of retinal pigment epithelial cells (ARPE19) and retinal ganglion cells (RGC5) were used. Bromodeoxyuridine incorporation, MTT assay, and scanning electron microscopy were performed. RESULTS: Injected TA sank slowly through the silicone oil and started to sediment below the silicone oil bubble shortly after injection. After the simulated intravitreal injection, no TA could be retrieved from the silicone oil bubble. In contrast, when a suspension of silicone oil and TA was prepared before injection, stable noncytotoxic amounts of TA (25 microg/mL) could be retrieved for up to 90 days. After mere injection (without previous suspension in silicone oil), the sedimented TA crystals showed a pronounced cytotoxic effect. CONCLUSIONS: Intravitreally injected TA does not mix with silicone oil. TA crystals that sediment at the lower border of a silicone oil bubble may be harmful to retinal cells. A suspension of TA in silicone oil may exhibit safer extended release over several days.

Assessment of the impact of dosing time on the pharmacokinetics/pharmacodynamics of prednisolone.

Prednisolone is widely used for the treatment of inflammation and auto-immune diseases. It exhibits nonlinear pharmacokinetics (PK); and its induced systemic effects (pharmacodynamics (PD)) are commonly evaluated with two biomarkers, cortisol and blood lymphocytes in plasma. Circadian patterns are observed in both biomarkers. Furthermore, the disease itself may show a circadian pattern. For example, in rheumatoid arthritis patients, better therapeutic outcomes have been reported when prednisolone was administered in the very early morning. The aim of this study is to evaluate the impact of dosing time on the PK/PD of prednisolone with a simulation approach using an interactive algorithm. A series of simulations were performed with either intravenous or oral administration of prednisolone or prednisone. The results showed that the initial or maximum concentration and trough concentration of total prednisolone were lower when the drug was administered in the early morning around 6 AM: . Oscillation patterns were observed in cumulative cortisol suppression (CCS) and alteration of total lymphocyte trafficking in blood. When the drug was given in the morning within the therapeutic dose range, or around 6 PM: for a small dose amount (<1 mg), the minimum CCS and maximum effect on lymphocytes were observed. These results indicated that the PK/PD of prednisolone are time- and dose-dependent, and suggested that it is necessary to consider the application of chronotherapy to achieve better clinical outcomes with fewer side effects of prednisolone, and a PK/PD simulation approach could provide a valuable tool to evaluate and predict time-dependency in the system.

Amphipathic weak acid glucocorticoid prodrugs remote-loaded into sterically stabilized nanoliposomes evaluated in arthritic rats and in a Beagle dog: a novel approach to treating autoimmune arthritis.

OBJECTIVE: The use of glucocorticoids (GCs) in rheumatoid arthritis is limited by side effects related to unfavorable pharmacokinetics and biodistribution. Liposomal GC formulations have been studied since the 1970s in an attempt to overcome this obstacle, but none has entered clinical use. We undertook this study to determine whether a novel approach could overcome the limitations that have thus far prevented the clinical use of these formulations: low drug:lipid ratio, low encapsulation efficiency, and lack of controlled release. METHODS: We used approximately 80-nm sterically stabilized (pegylated) nanoliposomes (NSSLs), which were remote-loaded with an amphipathic weak acid GC (such as methyl prednisolone hemisuccinate) utilizing an intraliposome (aqueous compartment)-high/extraliposome (bulk medium)-low transmembrane calcium acetate gradient. This unique method actually "traps" the GC in the liposomal aqueous phase as a calcium-GC precipitate. RESULTS: Our liposome formulation exhibited high encapsulation efficiency (94%) and a high drug:lipid mole ratio (0.41) and demonstrated controlled release of the encapsulated GC during systemic circulation and in inflamed paws in rats with adjuvant-induced arthritis. In addition, both in arthritic rats and in a Beagle dog, we showed the pharmacokinetic advantage of using liposomes as GC carriers. Finally, we demonstrated the superior therapeutic efficacy of our liposome formulation over that of free GCs in arthritic rats, both in early and in peak disease stages. CONCLUSION: Amphipathic weak acid GCs remote-loaded into approximately 80-nm NSSLs overcome past limitations of liposomal GC formulations. The unique loading method, which also leads to controlled release, improves the therapeutic effect both systemically and locally. Such a development has great potential for improving GC therapy.

Lack of pharmacokinetic interaction between St. John's wort and prednisone.

BACKGROUND: St. John's wort (SJW) is a popular dietary supplement involved in numerous dietary supplement-drug interactions with prescription and non-prescription drugs. The supplement has been shown to affect the metabolism of various CYP3A4 substrates. The CYP3A4 pathway mediates the metabolism of a large number of drug entities, including the corticosteroids prednisone and prednisolone. OBJECTIVE: To examine the effects of long-term SJW administration on the pharmacokinetics of prednisone and its reversible metabolite prednisolone in male subjects. METHODS: Eight male subjects participated in this single-dose study. The pharmacokinetics of prednisone and prednisolone were evaluated before and after 28 days of SJW administration. Plasma corticosteroid concentrations were determined using a normal phase high-performance liquid chromatography assay. Model-independent methods were used to evaluate corticosteroid pharmacokinetics. RESULTS: Twenty-eight days of SJW treatment resulted in no significant alterations in the pharmacokinetic parameters for prednisone or prednisolone. Oral administration of prednisone resulted in prednisone mean +/- SD area under the curves (AUCs) of 115.89 +/- 39.52 microg x h/L prior to SJW treatment and 128.76 +/- 32.71 microg x h/L after 28 days of treatment. Prednisolone mean AUCs were 714.19 +/- 153.29 microg x h/L before SJW administration and 700.74 +/- 89.68 microg x h/L after treatment. CONCLUSIONS: Concurrent administration of SJW had no significant effect on the single-dose pharmacokinetics of prednisone or metabolic prednisolone in male subjects.

Erythrocytes-mediated delivery of dexamethasone in steroid-dependent IBD patients-a pilot uncontrolled study.

BACKGROUND AND AIM: Autologous erythrocytes can be used as carriers of drugs, owing to the ability of their membrane to be opened and resealed under appropriate conditions. In this pilot uncontrolled study, we investigated efficacy and safety of dexamethasone-encapsulated erythrocytes in steroid-dependent IBD patients. MATERIALS AND METHODS: Ten patients (5 with ulcerative colitis and 5 with Crohn's disease) with steroid dependency ranging from 8 to 60 months were studied. Seven of them were in clinical remission, and the remaining three had mild activity. Eight patients were also under azathioprine or 6-MP for at least 6 months (range 6-24 months), while another two patients were intolerant to both drugs. Fifty milliliters of blood were drawn from each subject; dexamethasone 21-Phosphate (Dex 21-P) was encapsulated into erythrocytes by means of specially designed equipment, and drug-loaded erythrocytes were infused into original donors. The procedure was repeated after 4 and 8 wk, and patients were instructed to withdraw corticosteroids. RESULTS: A mean dose of 5.5+/-2.4 mg Dex 21-P was loaded in the erythrocytes at each treatment. Following re-infusion of loaded erythrocytes, plasma Dexamethasone (Dex) concentrations were detected after as long as 28 days. Steroids were completely withdrawn by the second month. After the third infusion, all patients, including the three with mild active disease, were in clinical remission. ESR levels dropped from 47+/-27 at baseline to 27+/-16 mm/h (p<0.02), and CRP levels from 1.6+/-1.3 to 0.6+/-0.5 mg/dl (p<0.02). After a mean follow-up of 12+/-3 months, six patients relapsed, and the remaining four patients remained in remission. Pre-existing steroid-related adverse effects disappeared during the follow-up. CONCLUSIONS: Loading of Dex 21-P in autologous erythrocytes is feasible and safe. The very low dose of Dex released in blood stream was able to maintain patients in clinical remission and allowed steroids withdrawal.

A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis.

A randomized, double blind, placebo-controlled multicentre clinical trial of 12 weeks' duration was undertaken in 60 dogs with atopic dermatitis to evaluate the steroid sparing effect of essential fatty acid supplementation. The dogs were randomly assigned to receive either a combination of borage seed oil and fish oil or a placebo, in addition to prednisolone tablets. All dogs received a standardized basal diet. Owners of the dogs recorded pruritus daily using a 10 cm visual analog scale and the dosage of prednisolone was established based on the pruritus score, according to written instructions. The dosage of prednisolone and the use of any concurrent treatment (shampoo and/or ear-cleanser) were recorded by the owner on a daily basis. The investigators graded the skin lesions at days 0, 42 and 84. The use of prednisolone during the test period was lower in the active group, but the difference was not statistically significant (P = 0.32). The test period was sequentially divided into 43-84, 50-84, 57-84, 64-84, 71-84 and 78-84 days. On day 64, the difference between the active group and the placebo group reached statistical significance (P = 0.04) with an increasing difference towards the end of the study. A statistically significant reduction in the pruritus scores and the total clinical scores from day 0 to day 84 was apparent in both groups (P < 0.0001). At the end of the study, both the pruritus score and the total clinical score were lower in the active group. Our findings indicate a steroid sparing effect of essential fatty acid supplementation in canine atopic dermatitis and, furthermore, that there is a time lag before the effect is attained.