Prednisolone Concentrations Research Articles

Photoinduced Chemiluminescence Determination of Prednisolone Using Lucigenin-Cobalt 5,10,15,20-Tetra(4-Pyridyl)-21H,23H-Porphine System.

Sensitive and precise assay of prednisolone, a steroid hormone, has received great attention due to its significant role in the treatment of a series of diseases. In this study, we have developed a simple, quick, and accurate technique in this part to measure prednisolone. Cobalt 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (CoTPyP) as a mimic peroxidase catalyzes the chemiluminescence (CL) reaction of lucigenin for the first time. CoTPyP has a great impact on the CL signal. Furthermore, the CL system has been successfully used for the prednisolone flow-injection test. The findings showed that the UV irradiation of prednisolone led to an unimolecular photochemical reaction that could enhance yield of high-energy intermediate and cause higher CL emission. Under ideal experimental circumstances, CL intensity was shown to be proportionate to prednisolone concentration in the range of 0.1-170 μg mL-1 (r = 0.9925, n = 4). A detection limit of 0.072 μg mL-1 was observed. Compared with the HPLC approach, our proposed method provides a sensitive, fast, and efficient analysis of prednisolone in pharmaceutical formulations and biological fluids.

Prednisolone pharmacokinetics in dogs with protein-losing enteropathy.

It is unknown if glucocorticoid malabsorption contributes to the approximate 50% treatment failure rate in dogs with protein-losing enteropathy (PLE). To compare pharmacokinetics (PK) of orally administered prednisolone in dogs with PLE vs healthy controls. Fourteen dogs with well-characterized PLE and 7 control dogs. Prospective case-controlled study. Dogs were treated with 1 mg/kg prednisolone PO once daily for approximately 3 weeks. Venous blood samples were collected at set timepoints before and after prednisolone administration on the first (T1) and final (T2) study days. Total and non-protein bound serum prednisolone concentrations were determined using liquid chromatography tandem-mass spectrometry, and pharmacokinetics variables were derived from the drug concentration data. Pharmacokinetics variables were compared between PLE and control dogs and between PLE short-term responders and non-responders. The PLE dogs had a shorter half-life of the terminal slope than control dogs (harmonic mean of 1.3 vs 1.8 hours; P = .05) whereas the percentage of serum prednisolone that was non-protein bound was higher in PLE dogs than in control dogs (median of 15.7% vs 6.7%; P = .02) at T1. Total prednisolone drug exposures and maximum total serum drug concentrations did not differ between PLE and control dogs at T1 or T2, nor did they differ between short-term responders and non-responders within the PLE population (P > .05 for all comparisons). Overall drug exposures are similar between PLE dogs and healthy controls. Glucocorticoid malabsorption is unlikely to be a common cause of treatment failure in dogs with PLE.

In vitro chemosensitivity testing of the feline large granular lymphocyte cell line (S87).

Feline large granular lymphocyte (LGL) lymphoma is an aggressive neoplasia characterised by short survival and poor response to chemotherapy. In this study, the effect of different chemotherapeutic agents on the growth kinetics of the feline cell line S87, a non-MHC-restricted feline LGL cell line, was investigated. Where possible, IC50 (inhibitory concentration 50) values were determined. The IC50 values of the cell line as lymphoma models can provide clues to the situation in vivo and serve as a basis for studying resistance mechanisms. Cells were incubated with various concentrations of vincristine, doxorubicin, 4-hydroperoxycyclophosphamide, prednisolone, methotrexate and L-asparaginase for 24 and 48h, respectively. The IC50 values could be determined as 14.57 (7.49-28.32) μg/mL at 24h incubation and 5.72 (4.05-8.07) μg/mL at 48h incubation for doxorubicin and 9.12 (7.72-10.76) μg/mL at 24h incubation and 4.53 (3.74-5.47) μg/mL at 48h incubation for 4-hydroperpoxycyclophosphamide. Treatment with vincristine and methotrexate resulted in relatively high cell resistance whereas L-asparaginase and prednisolone treatment led to a reduction in cell number compared to control while cell viability was not affected (cytostatic effect). Overall, the feline LGL cell line S87 proves to be relatively sensitive to doxorubicin and 4-hydroperoxycyclophosphamide and relatively resistant to treatment with vincristine, prednisolone, methotrexate and L-asparaginase. The results of this study can be used for further investigations on resistance mechanisms in feline LGL lymphoma. Doxorubicin and cyclophosphamide can be interpreted as promising candidates for the therapy of feline LGL lymphomas.

The combined treatment of gold nanoparticles associated with photobiomodulation accelerate the healing of dermonecrotic lesion

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion. Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis. Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema. Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.

Development and optimization of an in-house heterologous ELISA for detection of prednisolone drug in enzyme conjugates using spacers.

The introduction of spacers in coating steroid protein complexes and/or enzyme conjugates or immunogens is known to exert an influence on the sensitivity of steroid enzyme immunoassays. We investigated the impact of different homobifunctional spacers, ranging in atomic length from 3 to 10, on the sensitivity and specificity of prednisolone (PSL) enzyme immunoassays. In this study, four homo-bifunctional spacers, namely, carbohydrazide (CH), adipic acid dihydrazide (ADH), ethylene diamine (EDA), and urea (U), were incorporated between PSL and horseradish peroxidase (HRP) for preparing the enzyme conjugate with an aim to improve the sensitivity of the assay without compromising assay specificity. The assays were developed using these enzymes conjugated with antibodies raised against the PSL-21-HS-BSA immunogen. The sensitivity of the PSL assays after insertion of a bridge in the enzyme conjugate was 1.22 ng/mL, 0.59 ng/mL, 0.48 ng/mL, and 0.018 ng/mL with ADH, CH, EDA, and urea as a spacer, respectively. Among the four combinations, the PSL-21-HS-BSA-antibody with PSL-21-HS-U-HRP-enzyme conjugate gave better sensitivity and less cross-reaction. The percent recovery of PSL from the exogenously spiked human serum pools was in the range of 88.32%-102.50%. The intra and inter-assay CV% was< 8.46%. The PSL concentration was estimated in the serum samples of patients on PSL treatment. The serum PSL values obtained by this method correlated well with the commercially available kit (r2 = 0.98). The present study suggests that the nature of the spacer is related to assay sensitivity and not the spacer length.

Optimising prednisolone or prednisone replacement in adrenal insufficiency.

Patients with adrenal insufficiency (AI) have higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times. The cortisol circadian rhythm is difficult to mimic with twice or thrice-daily hydrocortisone. Prednisolone is a once-daily alternative which may improve patient compliance and convenience. Prednisolone day curves can be used to accurately down-titrate patients to the minimum effective dose. We aimed to review prednisolone day curves and determine therapeutic ranges at different timepoints after administration. Between August 2013 and May 2021, 108 prednisolone day curves from 76 individuals receiving prednisolone replacement were analysed. Prednisolone concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Spearman's correlation coefficient was used to determine the relationship between 2-, 4- and 6-hour prednisolone levels compared to the validated standard 8-hour prednisolone level (15-25 μg/L). The median dose was 4mg prednisolone once daily. There was strong correlation between the 4-hour and 8-hour (R=0.8829, p ≤0.0001), and 6-hour and 8-hour prednisolone levels (R=0.9530, p ≤ 0.0001). Target ranges for prednisolone were 37-62 μg/L at 4-hours, 24-39 μg/L at 6-hours and 15-25 μg/L at 8-hours. Prednisolone doses were successfully reduced in 21 individuals and of these, three were reduced to 2mg once daily. All patients were well upon follow-up. This is the largest evaluation of oral prednisolone pharmacokinetics in humans. Low dose prednisolone of 2-4mg is safe and effective in most patients with AI. Doses can be titrated with either 4-hour, 6-hour, or 8-hour single timepoint drug levels.

Urinary glucocorticoids in harbour seal (Phoca vitulina) pups during rehabilitation

The glucocorticoid (GC) hormone cortisol is often measured in seals to indicate their stress levels, although other endogenous GCs are usually overlooked. We investigated concentrations of four endogenous GCs in the urine of “orphan” harbour seal pups in rehabilitation. We hypothesised that the GC levels would be elevated if pups were socially isolated, without water access, and with low body mass. Ninety-six samples were collected from 32 pups at four different rehabilitation centres and were analysed by Ultra Performance Liquid Chromatography and Tandem Mass Spectrometry. Median urinary creatinine (Cr) concentrations of endogenous prednisolone (31.6 ng/mg/Cr) and prednisone (31.1 ng/mg/Cr) occurred in similar magnitude to cortisol (37.0 ng/mg/Cr), while median cortisone concentrations were higher (390 ng/mg/Cr). Prednisolone and prednisone concentrations were more strongly inversely related to pup growth rate and pup mass than cortisol and cortisone. Concentrations of all four GCs decreased with mass gain for pups with water access but did not decrease for pups without water; linear mixed models indicated the interaction between these trends was significant for cortisol and cortisone, but not for prednisolone or prednisone. These results indicate the potential value of measuring all four of these endogenous GC hormones in phocid seal pups.

Clinical Evidence on the Purported Pharmacokinetic Interactions between Corticosteroids and Mycophenolic Acid.

Corticosteroids (steroids) are commonly used concurrently with mycophenolic acid (MPA) as the first-line immunosuppression therapy for the prevention of rejection in solid organ transplantations. Steroids are also commonly administered with MPA in various autoimmune disorders such as systemic lupus erythematosus and idiopathic nephrotic syndrome. Despite various review articles having suggested the presence of pharmacokinetic interactions between MPA and steroids, definitive data have not yet been demonstrated. The aim of this Current Opinion is to critically evaluate the available clinical data and propose the optimal study design for characterising the MPA-steroid pharmacokinetic interactions. The PubMed and Embase databases were searched for relevant clinical articles in English as of September 29, 2022, where a total of 8 papers have been identified as supporting and 22 as non-supporting the purported drug interaction. To objectively evaluate the data, novel assessment criteria to effectively diagnose the interaction based on known MPA pharmacology were formulated, including the availability of independent control groups, prednisolone concentrations, MPA metabolite data, unbound MPA concentrations, and the characterisations of entero-hepatic recirculation and MPA renal clearance. Overall, the majority of the identified corticosteroid data were pertaining to prednisone or prednisolone. Our assessment indicated that no conclusive mechanistic data supporting the interaction are available in the current clinical literature, and further studies are required to quantify the effects/mechanisms of steroid-tapering or withdrawal on MPA pharmacokinetics. This current opinion provides justification for further translational investigations, as this particular drug interaction has the potential to exert significant adverse outcomes in patients prescribed MPA.

Fingerprick Microsampling Methods Can Replace Venepuncture for Simultaneous Therapeutic Drug Monitoring of Tacrolimus, Mycophenolic Acid, and Prednisolone Concentrations in Adult Kidney Transplant Patients.

Kidney transplant patients undergo repeated and frequent venepunctures during allograft management. Microsampling methods that use a fingerprick draw of capillary blood, such as dried blood spots (DBS) and volumetric absorptive microsamplers (VAMS), have the potential to reduce the burden and volume of blood loss with venepuncture. This study aimed to examine microsampling approaches for the simultaneous measurement of tacrolimus, mycophenolic acid, mycophenolic acid glucuronide (MPAG), and prednisolone drug concentrations compared with standard venepuncture in adult kidney transplant patients. DBS and VAMS were simultaneously collected with venepuncture samples from 40 adult kidney transplant patients immediately before and 2 hours after immunosuppressant dosing. Method comparison was performed using Passing-Bablok regression, and bias was assessed using Bland-Altman analysis. Drug concentrations measured through microsampling and venepuncture were also compared by estimating the median prediction error (MPE) and median absolute percentage prediction error (MAPE). Passing-Bablok regression showed a systematic difference between tacrolimus DBS and venepuncture [slope of 1.06 (1.01-1.13)] and between tacrolimus VAMS and venepuncture [slope of 1.08 (1.03-1.13)]. Tacrolimus values were adjusted for this difference, and the corrected values showed no systematic differences. Moreover, no systematic differences were observed when comparing DBS or VAMS with venepuncture for mycophenolic acid and prednisolone. Tacrolimus (corrected), mycophenolic acid, and prednisolone microsampling values met the MPE and MAPE predefined acceptability limits of <15% when compared with the corresponding venepuncture values. DBS and VAMS, collected in a controlled environment, simultaneously measured multiple immunosuppressants. This study demonstrates that accurate results of multiple immunosuppressant concentrations can be generated through the microsampling approach, with a preference for VAMS over DBS.

SENSOR PARA DETECÇÃO DE PREDNISOLONA NO DOPING ESPORTIVO

ABSTRACT Introduction: Prednisolone causes pro-inflammatory impulses to be inhibited and anti-inflammatory signals to be promoted. As a result, it alters how the body's immune system reacts to certain diseases. The World Anti-Doping Agency, however, has banned SNP and other glucocorticosteroids. An electrochemical sensor can be developed using a gold nanocomposite, polypyrrole nanoparticles and synthesized carbon nanotubes (Au-PPy NPs@CNTs). Objective: Develop an electrochemical sensor to detect prednisolone. Method: Au-PPy NPs@CNTs nanocomposite was chemically synthesized with a modified glassy carbon electrode (GCE) surface. Results: According to SEM data, the nanocomposite was composed of amorphous Au NPs, and PPy NPs deposited in tubes strongly entangled in a CNTs network. The wide linear range and low detection limit of the Au-PPy NPs@CNTs/GCE as prednisolone sensors were attributed to the combined catalytic performance of the Au and PPy NPs@CNTs nanostructures. Conclusion: The results of prednisolone detection in each specimen using the amperometric method indicated good accuracy. The accuracy and precision of Au-PPy NPs@CNTs/GCE for prednisolone detection were explored in blood samples from 5 young athletes aged 20-24 years who used prednisolone tablets (RSD less than 4.25%). In addition to monitoring prednisolone concentrations in athletes’ serum, Au-PPy NPs@CNTs/GCE can be used as a reliable prednisolone sensor. Level of evidence II; Therapeutic studies - investigating treatment outcomes.

Prednisolone pharmacokinetics after oral prednisone administration in paediatric patients with kidney transplant.

Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure-safety relationships. Ninety-seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.4-17.2years) in order to investigate prednisone PPK. We selected children receiving oral prednisone as part of their immunosuppressive regimen. A PPK analysis was performed using Monolix. A 1-compartment model best described prednisolone concentrations. Large IIV was observed as prednisolone was undetectable at H12 in some patients but could still be detected at H24 in others. Both bodyweight and ciclosporin cotreatment influenced the PK. The clearance (CLU ) and volume of distribution of free prednisolone allometrically scaled to 70 kg were 27.6L/h and 101 L. Ciclosporin cotreatment decreased CLU by 67%. High blood pressure and new onset diabetes after transplantation were associated with daily free prednisolone exposure. This study is the first analysis of prednisolone PPK in kidney-transplanted children. Some of the IIV in the PK parameters was explained by bodyweight and ciclosporin cotreatment. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy and limit side effects. The use of therapeutic drug monitoring in kidney-transplanted children may be useful, especially with respect to safety issues.

Evaluation of prednisolone and prednisolone sodium succinate concentrations in human plasma and inner ear perilymph during cochlear implantation 24 h after intratympanic injection

Background The use of intratympanic (IT) steroids has drastically increased over the past 10–15 years to manage many otological pathologies. Objectives This study aimed to compare the concentrations of prednisolone and prednisolone sodium succinate (SS) in the plasma and inner ear perilymph of participants who underwent cochlear implantation 24 h after IT injection. Materials and methods It was a prospective comparative randomized study. Twenty participants received an IT injection of prednisolone SS ∼24 h before the cochlear implantation. The other five participants received an IT saline injection and represented the control group. Perilymph and blood were sampled during the cochlear implantation surgery. Results Both prednisolone and prednisolone SS were still present in perilymph ∼24 h after the IT administration. Only prednisolone was present in the blood plasma of seven participants (35%). Conclusion IT injection of prednisolone SS resulted in high perilymph concentrations of prednisolone and prednisolone SS, which could stay in the perilymph for at least 24 h. Using a mini-endoscope during the IT injection may effectively detect barriers infront of the round window membrane, increasing the drug concentration in the inner ear. Significance IT injection is an effective method for delivering prednisolone to the inner ear.

Effect of prednisolone and saireito co-administration on T-cells of rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoimmune disease. Methotrexate (MTX) and prednisolone (PSL) are used in combination for severe RA therapy. However, it can increase the risk of osteoporosis and osteonecrosis. Saireito (114) can be used to reduce PSL dose owing to its immunosuppressive effects. However, the effect of combination therapy of PSL+114 on the immune system of RA patients remains unknown. This study compared the effect of PSL alone and PSL+114 on peripheral blood mononuclear cell (PBMC) proliferation, T-cell subsets, and cytokine production in adult RA patients receiving MTX monotherapy. We isolated PBMCs from 14 consenting RA patients, and cultured them with PSL (0.0001-1.0 μM) in combination with or without 114 (300 μg/mL) for 96 h in the presence of concanavalin A. We measured the proliferation rates of PBMC, proportions of CD4+, CD8+, and CD4+CD25+Foxp3+T-cells (induced T-regulatory cells), and concentrations of interferon-γ, interleukin (IL)-6, IL-10, IL-17A, and tumour necrosis factor in the culture supernatant. Compared to the blank, the PBMC proliferation rate significantly decreased at a reduced PSL concentration after 114 administration. The 50% inhibition concentration was 0.43 μM PSL for the PSL-only group as compared to 0.29 μM PSL for the PSL+114 co-administration group. The PSL+114 co-administration group had a significantly higher concentration of IL-6 compared to the PSL-only group. The use of 114 in combination with low-concentration PSL intensified its immunosuppressive effect. However, the concentration of IL-6 was elevated in the co-administration group, suggesting exacerbation of RA activity.

Primary studies on biotransformation of steroidal drug Prednisolone

The less biodegradable steroidal drug, Prednisolone is one of the widely used drugs in the treatment of autoimmune and infectious diseases. Transformation of prednisolone can be achieved with microbial activity. Isolation of prednisolone-resistant microorganisms was done using a sewage sample. Out of 5 isolates, one isolate was selected for further studies based on maximum tolerability to prednisolone. The isolate was identified based on MALDI-TOF. The strain was found to have a match score of 2.336 with gram-negative bacteria Klebsiella pneumoniae spp pneumoniae DSM3010 4T HAM. The isolate was found to degrade 80% prednisolone on the 5th day of fermentation. The concentration of prednisolone was determined using a colorimetric-based method and HPLC technique.

What Is the Impact of Dexamethasone and Prednisolone Glucocorticoids on the Structure of Meiobenthic Nematode Communities?

The toxic effects of two commonly used glucocorticoids, the dexamethasone and prednisolone, on meiobenthic nematodes were assessed in a laboratory experiment for 30 days. Nine treatments were employed, comprised of two single and mixed concentrations of dexamethasone and prednisolone (i.e., 0.14 and 1.4 µg·L−1). The exposure to both glucocorticoids showed significant effects on the abundance and taxonomic diversity of nematodes. Such changes were mainly induced by the decrease in the abundance of the species Microlaimus honestus, considered to be sensitive to prednisolone and by the increase in Enoplolaimus longicaudatus abundance, which can be considered tolerant. The exposure to these glucocorticoids also led to a decrease in 2A feeding groups, 2–4 mm body-size interval, and c-p3 life history type in most treatments, with type of life history and shape of amphids as the most relevant functional traits impacted by these two glucocorticoids. The results could also be explained by the potential antagonism between these two pharmaceuticals.

Prednisolone and dexamethasone are systemically absorbed after topical application of ophthalmic suspensions in healthy dogs.

To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. 12 purpose-bred Beagles. Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

Screening for drugs potentially interfering with MCT8-mediated T3 transport in vitro identifies dexamethasone and some commonly used drugs as inhibitors of MCT8 activity.

Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. Dexamethasone significantly inhibited T3 uptake at 10μM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50μM and 68% at 100μM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10μM. L-Carnitine inhibited T3 uptake only at 500mM and 1M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids.

SummaryBackgroundTopical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species.ObjectivesTo investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum.Study designProspective randomised experimental pharmacokinetic study.MethodsTwenty‐one Shetland ponies without ophthalmic disease were treated bilaterally topically every 2 hours during 24 hours to obtain steady state drug concentrations. One eye was treated with 0.15 mg of dexamethasone disodium phosphate (0.1%), and the other eye was simultaneously treated with 1.5 mg of prednisolone acetate (1%). Serum samples were taken prior to the induction of general anaesthesia. Aqueous and vitreous humour samples were taken during euthanasia at time points after administration of the last dose (t = 5 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min). Each pony was randomly assigned to one time point, and three ponies were sampled per time point. Dexamethasone and prednisolone concentrations were measured by liquid chromatography‐mass spectrometry.ResultsThe mean dexamethasone concentration in aqueous humour was 32.4 ng/mL (standard deviation [SD] 10.9) and the mean prednisolone concentration was 321.6 ng/mL (SD 96.0). In the vitreous and in serum samples concentrations of both corticosteroids were below the limit of detection (LOD 2.5 ng/mL).Main limitationsThe study group was limited to subjects without evidence of current ophthalmic disease. A limited number of time points were measured.ConclusionsPotentially effective dexamethasone and prednisolone concentrations were measured in the anterior chamber, but vitreal concentrations were negligible. Systemic uptake was low. Therefore, treatment with only topically administered corticosteroids is deemed insufficient in horses in cases of posterior uveitis. Further studies evaluating other routes of administration are warranted.

Pharmacokinetics of Orally Administered Prednisolone in Alpacas.

This study aimed to determine the pharmacokinetics of prednisolone following intravenous and oral administration in healthy adult alpacas. Healthy adult alpacas were given prednisolone (IV, n = 4), as well as orally (PO, n = 6). Prednisolone was administered IV once (1 mg/kg). Oral administration was once daily for 5 days (2 mg/kg). Each treatment was separated by a minimum 4 month washout period. Samples were collected at 0 (pre-administration), 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, and 24 h after IV administration, and at 0 (pre-administration), 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24 after the first and 5th PO administration. Samples were also taken for serial complete blood count and biochemistry analysis. Prednisolone concentration was determined by high pressure liquid chromatography. Non-compartmental pharmacokinetic parameters were then determined. After IV administration clearance was 347 mL/kg/hr, elimination half-life was 2.98 h, and area under the curve was 2,940 h*ng/mL. After initial and fifth oral administration elimination half-life was 5.27 and 5.39 h; maximum concentration was 74 and 68 ng/mL; time to maximum concentration was 2.67 and 2.33 h; and area under the curve was 713 and 660 hr*ng/mL. Oral bioavailability was determined to be 13.7%. Packed cell volume, hemoglobin, and red blood cell counts were significantly decreased 5 days after the first PO administration, and serum glucose was significantly elevated 5 days after the first PO administration. In conclusion, serum concentrations of prednisolone after IV and PO administration appear to be similar to other veterinary species. Future research will be needed to determine the pharmacodynamics of prednisolone in alpacas.

Potentiometric Determination of Prednisolone in Pharmaceutical Formulations

In this present work, a prednisolone ion selective electrode (PRED-ISE) has been developed. The electrode shows linear response towards prednisolone in the range 3.0×10−6 – 8.6×10−3 M with a detection limit of 2.5×10−6. PRED-ISE was used as an indicator electrode for the potentiometric titration of different concentrations of standard prednisolone against standardized sodium tetraphenyl borate solution and in tablets. The electrode manifests advantages of low resistance, fast response and, most importantly, good selective relativity to a variety of other cations.