Betamethasone Research Articles

Enhanced degradation of glucocorticoids, a potential COVID-19 remedy, by co-fermentation of waste activated sludge and animal manure: The role of manure type and degradation mechanism

Waste activated sludge (WAS) and animal manure are two significant reservoirs of glucocorticoids (GCs) in the environment. However, GC degradation during anaerobic digestion (AD) of WAS or animal manure has rarely been investigated. In this study, co-fermentation of WAS and animal manure was conducted to investigate the performance of AD in controlling GC dissemination. Effects of manure type on GC degradation and sludge acidification were investigated. The results showed that co-fermentation of WAS and chicken manure (CM) significantly enhanced the degradation of hydrocortisone (HC) to 99%, betamethasone (BT) to 99%, fluocinolone acetonide (FA) to 98%, and clobetasol propionate (CP) to 82% in 5 days with a mixing ratio of 1:1 (g TS sludge/g dw manure) at 55 °C and initial pH of 7. Simultaneously, sludge reduction was increased by 30% and value-added volatile fatty acid (VFA) production was improved by 40%. Even a high GC content of biomass (3.6 mg/g TS) did not impact both sludge hydrolysis and acidification. The amendment of WAS with CM increased soluble organic carbon, Ca2+, and relative abundance of anaerobes (Eubacterium) associated with organic compound degradation. Furthermore, 44 transformation products of HC, BT, FA, and CP with lower lipophilicity and toxicity were identified, indicating possible degradation pathways including hydroxylation, ketonization, ring cleavage, defluorination, hydrogenation, methylation, and de-esterification. Overall, this study provides a practical way to control GC pollution and simultaneously promote waste reduction and VFA production. Animal manure type as an overlooked factor for influencing co-fermentation performance and pollutant degradation was also highlighted.

Degradation of glucocorticoids in water by a synergistic system of peroxymonosulfate, microbubble and dielectric barrier discharges

Glucocorticoids (GCs) in the environment have been an increasing concern. Most recently, GCs have been shown to be an effective remedy to manage septic shock in patients infected with COVID-19. In this study, a self-made dielectric barrier discharge reactor integrating microbubbles and peroxymonosulfate (DBD/MB/PMS) was used to degrade the GCs in water. At neutral pH and ambient temperature, hydrocortisone (HC), betamethasone (BT) and fluocinolone acetonide (FA) were degraded effectively by the DBD/MB/PMS system with the 90-min degradation efficiencies of 77%, 80% and 82%, respectively (discharge power: 83.5 W; PMS:GC ratio: 20:1). In comparison, the 90-min degradation efficiencies for HC, BT and FA by DBD/MB system (discharge power: 83.5 W, pH unadjusted, flow rate 40 mg/L) were only 49%, 54% and 60% respectively; and the efficiencies by heat activated PMS (90 °C) were only 24%, 12%, and 16%, respectively. Hence, DBD/MB is an efficient approach for PMS activation, which resulted in increased removal efficiencies and energy yields for GCs degradation. The rate constants for GCs degradation also increased with the increase of PMS dosage and initial solution pH. Both SO4− and OH were prominent species for GCs degradation. Based on the results of scavenging experiment, the contributions of SO4− for HC, BT and FA degradation were roughly estimated to be 51%, 59% and 60%, respectively, and the contributions of OH were 30%, 29% and 27%, respectively. This work not only provides a novel approach in dealing with GCs contaminated water, but also highlights the synergistic effect of plasma, MB and PMS.

Population pharmacodynamic modeling of intramuscular and oral dexamethasone and betamethasone effects on six biomarkers with circadian complexities in Indian women

Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and betamethasone (BET) in 48 healthy nonpregnant Indian women in a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM) where each woman enrolled in a two-period cross-over study. Plasma concentrations collected over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Overall, BET exhibited slower clearance, similar volume of distribution, faster absorption, and longer persistence than DEX with BET acetate producing extremely slow absorption but full bioavailability of BET. Six biomarkers were assessed over a 24-h baseline period with four showing circadian rhythms with complex baselines. These baselines and the strong responses seen after drug dosing were fitted with various indirect response models using the Laplace estimation methods in NONMEM 7.4. Both the PK and six biomarker responses were well-described with modest variability likely due to the homogeneous ages, weights, and ethnicities of the women. The drugs either inhibited or stimulated the influx processes with some models requiring joint inclusion of drug effects on circadian cortisol suppression. The biomarkers and order of sensitivity (lowest IC50/SC50 to highest) were: cortisol, T-helper cells, basophils, glucose, neutrophils, and T-cytotoxic cells. DEX sensitivities were generally greater than BET with corresponding mean ratios for these biomarkers of 2.86, 1.27, 1.72, 1.27, 2.69, and 1.06. Overall, the longer PK (e.g. half-life) of BET, but lesser PD activity (e.g. higher IC50), produces single-dose response profiles that appear quite similar, except for the extended effects from BET-PA. This comprehensive population modeling effort provides the first detailed comparison of the PK profiles and six biomarker responses of five commonly used dosage forms of DEX and BET in healthy women.

TiO2-Photocatalyzed Water Depollution, a Strong, yet Selective Depollution Method: New Evidence from the Solar Light Induced Degradation of Glucocorticoids in Freshwaters

The photodegradation of the most prescribed glucocorticoids (GCs) was studied under relevant environmental conditions in the presence of suspended TiO2. The considered drugs included cortisone (CORT), hydrocortisone (HCORT), betamethasone (BETA), dexamethasone (DEXA), prednisone (PRED), prednisolone (PREDLO), and triamcinolone (TRIAM). The experiments were carried out at concentrations (50 µg L−1) close to the real ones in freshwater samples (tap and river) under simulated and natural sunlight, and their decomposition took place very efficiently under natural sunlight. The reactions were monitored by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). According to a pseudo-first-order decay, all drugs underwent degradation within 15 min, following different paths with respect to the direct photolysis. The observed kinetic constants, slightly lower in river than in tap water, varied from 0.29 to 0.61 min−1 with modest differences among GCs in the same matrix. Among main matrix macro-constituents, humic acids (HAs) were the most interfering species involved in GCs degradation. The photogenerated primary products were identified by HPLC-ESI-MS/MS, allowing to elucidate the general photochemical path of GCs. Finally, a comparison with literature data obtained using different advanced oxidation processes (AOPs) highlights the treatment efficiency with TiO2/solar light for removing such persistent aquatic contaminants.

Insights into the retention behavior of betamethasone by nanofiltration – An alternative for decentralized drinking water treatment

Betamethasone (BET) has been found in surface and wastewater around the world. The pharmaceutical is prescribed to human and veterinary use due to its anti-inflammatory, anti-allergic and immunosuppressive properties. As a result of its recalcitrant character and resistance to biological degradation processes, BET is not retained by wastewater treatment plant, nor in drinking water treatment plants. However, it is necessary to invest in techniques that allow BET to be removed from aqueous matrices in view of its adverse effect on human health and the environment. In this sense, nanofiltration (NF) stands out as a promising alternative. Thus, in this study, the DK NF membrane was applied under different transmembrane pressure (TMP; 4–10 bar) and feed flow rates (0.8–3.2 L/min) for surface water treatment, aiming for a higher permeate flux, as well as the higher BET retention. Increasing TMP lead to higher permeate flux (47.44 L/m2.h) and lower flux decline (J/J0 = 0.95). The increase in feed flow rates besides lead to a high permeate flux also contributed to a high membrane rejection (BET retention of 98.8%), but implies a higher specific energy consumption. The NF Opex was estimated in 0.43 US$/m3, which demonstrates that NF could be a feasible alternative to remove BET from drinking water with high desalination capacity.

Glucocorticoids in Freshwaters: Degradation by Solar Light and Environmental Toxicity of the Photoproducts.

The photodegradation process of seven glucocorticoids (GCs), cortisone (CORT), hydrocortisone (HCORT), betamethasone (BETA), dexamethasone (DEXA), prednisone (PRED), prednisolone (PREDLO) and triamcinolone (TRIAM) was studied in tap and river water at a concentration close to the environmental ones. All drugs underwent sunlight degradation according to a pseudo-first-order decay. The kinetic constants ranged from 0.00082 min−1 for CORT to 0.024 min−1 for PRED and PREDLO. The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The main steps of the degradation pathways were the oxidative cleavage of the chain 17 for CORT, HCORT and the rearrangement of the cyclohexadiene moiety for the other GCs. The acute and chronic toxicity of GCs and of their photoproducts was assessed by the V. fischeri and P. subcapitata inhibition assays. The bioassays revealed no significant differences in toxicity between the parent compounds and their photoproducts, but the two organisms showed different responses. All samples produced a moderate acute toxic effect on V. fisheri and no one in the chronic tests. On the contrary, evident hormesis or eutrophic effect was produced on the algae, especially for long-term contact.

The Antioxidant, Anti-Apoptotic, and Proliferative Potency of Argan Oil against Betamethasone-Induced Oxidative Renal Damage in Rats.

Simple SummaryThe present study aimed to investigate the protective effect of argan oil against nephrotoxic effect following overdose and long-term administration of betamethasone. The results revealed that betamethasone induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and marked thrombocytopenia. Moreover, betamethasone caused significant increase of serum urea and creatinine levels; renal malondialdehyde and nitric oxide contents associated with significant decrease of reduced glutathione content. Betamethasone also caused vascular, degenerative, and inflammatory histopathological alterations in kidney tissue along with increase of Bax and caspase-3 expressions and decrease of B-cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions. Conversely, the concomitant administration of argan oil (0.5, 1 mL/kg) with betamethasone ameliorated the aforementioned hematological, biochemical, pathological, and histochemical adverse effects. In conclusion, overdose and long-term administration of betamethasone could induce hematological changes and severe renal damage mediated by oxidative, apoptotic and proliferative mechanisms via increasing renal functions biomarkers and altering oxidant/antioxidant status along with pathological lesions and imbalance of Bax/Bcl-2 ratio that positively correlates with up-regulation of caspase-3 and down-regulation of PCNA in kidney tissue. However, argan oil could potentially protect against betamethasone- induced renal damage, in a dose-dependent manner, via its antioxidant, anti-apoptotic and proliferative properties.The present study aimed to investigate the protective effect of argan oil (AO) against nephrotoxic effects following overdose and long-term administration of betamethasone (BM). The phytochemical compositions of AO were assessed using GC/MS. Forty eight male Wister albino rats were divided into six groups and treated for 3 successive weeks. The control group was orally administrated distilled water daily, the BM group received BM (1 mg/kg, IM, day after day), AO/0.5 and AO/1 groups received AO (0.5 mL/kg, 1 mL/kg, orally, daily, respectively), BM + AO/0.5 group and BM + AO/1 group. The results revealed that BM induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and thrombocytopenia. Moreover, BM caused a significant increase of serum urea and creatinine levels, and renal malondialdehyde and nitric oxide contents with significant decrease of reduced glutathione content. BM also caused vascular, degenerative, and inflammatory histopathological alterations in kidney, along with an increase in the Bax/Bcl-2 ratio, activation of caspase-3, and decrease of proliferating cell nuclear antigen expression. Conversely, the concomitant administration of AO (0.5, 1 mL/kg) with BM ameliorated the aforementioned hematological, biochemical, pathological, and histochemical BM adverse effects. In conclusion, AO has protective effects against BM-induced renal damage, possibly via its antioxidant, anti-apoptotic, and proliferative properties.

Elimination profiles of betamethasone after different administration routes: Evaluation of the reporting level and washout periods to ensure safe therapeutic administrations.

Betamethasone (BET) is prohibited in sports competitions when administered by systemic routes, and it is allowed by other routes for therapeutic purposes. In out-of-competition periods, there is no restriction of use. The present work aimed to assess the urinary excretion of BET and its metabolites after allowed and prohibited administrations to verify the suitability of the current reporting level of 30 ng/ml used to distinguish allowed and prohibited administrations and to establish washout periods for oral and intramuscular (IM) administrations when out-of-competition treatments are needed. BET was administered to healthy volunteers by different routes: topical (10 mg/day for 5 days, n = 6 males), intranasal (320 μg/day for 3 days, n = 4 males and 4 females), oral (0.5 mg, n = 8 males) or IM (6 mg, n = 6 males, or 12 mg, n = 4 males and 4 females). Urine and plasma samples collected before and after administration were analysed using liquid chromatography-tandem mass spectrometry. Among all studied metabolites, the parent drug was selected as the best discriminatory marker. After topical administration, BET concentrations were lower than 6.6 ng/ml. However, after intranasal treatment, some samples at concentrations close to or higher than 30 ng/ml were detected, suggesting the need to revise the current reporting level. Urinary concentrations after oral and intranasal administrations were similar, and after IM administration, concentrations were much higher. Taking into account all information, a urinary reporting level of 60 ng/ml is proposed. Washout periods of at least 48 and 96 h are recommended after oral and IM administrations, respectively.

Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model

Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV infection, have an immune quiescent phenotype defined by...

Solubility Enhancement of Betamethasone, Meloxicam and Piroxicam by Use of Choline-Based Deep Eutectic Solvents

Background: The low aqueous solubility of three important drugs (betamethasone (BETA), meloxicam (MEL) and piroxicam (PIR)) have been increased by use of deep eutectic solvents (DESs) based choline chloride/urea (ChCl/U), choline chloride/ethylene glycol (ChCl/EG) and choline chloride/glycerol (ChCl/G) as new class of solvents at T = (298.15 to 313.15) K. Methods: DESs were prepared by combination of the ChCl/EG, U and G with the molar ratios: 1:2. The solubility of drugs in the aqueous DESs solutions was measured at different temperatures with shake flask method. Results: The solubility of the investigated drugs increased with increasing the weight fraction of DESs. The solubility data were correlated by e-NRTL and Wilson models. Also, the thermodynamic functions, Gibbs energy, enthalpy, and entropy of dissolution were calculated. Conclusion: At the same composition of co-solvents and temperature, the BETA, PIR and MEL solubility was highest in (ChCl/U + water), (ChCl/U + water) and (ChCl/EG + water) respectively. The calculated solubility based on these models was in good agreement with the experimental values. In addition, the results show that, the main contribution for drugs solubility in the aqueous DES solutions is the enthalpy.

Long-Term Proactive Management of Psoriasis Vulgaris with Fixed-Dose Combination of Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Foam: Results from a Phase III Randomized Controlled Trial

Abstract not available.

Imaging clinical case

Case report: The authors present the case of a 15-year-old adolescent boy with occipital spur noticed since the previous year and with progressive enlargement. No history of trauma or other associated symptoms was evident. Physical examination showed a hard tumefaction with no inflammatory signs and x-ray revealed occipital hyperostosis. The boy spent most free time playing with mobile gadgets, with poor body posture.Discussion/Conclusion: Although considered a normal feature, occipital spur in adolescents and young adults may be linked to poor posture, for instance associated with prolonged use of handheld technology. Exaggerated technology use may be associated with several complaints and musculoskeletal symptoms should not be neglected.

Обзор сравнительного микробиологического исследования оригинального и генерического препаратов (бетаметазон+ гентамицин+клотримазол)

Обзор сравнительного микробиологического исследования оригинального и генерического препаратов (бетаметазон+ гентамицин+клотримазол)

Simultaneous determination of plasma betamethasone disodium phosphate and betamethasone in rabbit by high performance liquid chromatography

Betamethasone disodium phosphate (BDP), a hydrophilic prodrug of betamethasone (BTM), was rapidly converted into betamethasone in blood following intravenous administration. In this study, we established an analytical method of high performance liquid chromatography (HPLC) to simultaneously determine BDP and its free base BTM in plasma samples. The calibration curves demonstrate good linearity (BDP, R2 = 0.99999; BTM, R2 = 0.99997) and reproducibility within a range from 50 ng/mL to 6000 ng/mL. The analytical method was applied to determine the pharmacokinetics of BTM and BDP following intravenous bolus injection of BDP in New Zealand white rabbits (0.4 mg/kg). The determined pharmacokinetic parameters were listed as follows: for BDP, half-life: 13.69 ± 2.70 min (Mean ± SEM, n = 6), clearance: 3.96 ± 0.45 mL/min/kg and distribution volume: 72.9 ± 9.67 mL/kg; for BTM, half-life: 228.58 ± 72.9 min, clearance: 3.50 ± 1.18 mL/min/kg, and distribution volume: 327.57 ± 69.9 mL/kg. The established HPLC analytical method and related pharmacokinetic parameters of BDP and BTM might be potentially applied to use these drug administration in the treatment of respiratory relevant diseases.

Pharmacokinetics of betamethasone disodium phosphate-loaded microparticle following pulmonary delivery

Pharmacokinetics of betamethasone disodium phosphate-loaded microparticle following pulmonary delivery

Oral B-blockers versus intralesional corticosteroids in treatment of infantile cutaneous hemangiomas

Aim Infantile hemangioma (IH) is one of the most common benign tumors of childhood, with an incidence of between 4 and 10%. Multiple modalities for treatment for IH were proposed, most commonly B-blockers and corticosteroids. Our study objective was to compare between oral B-blockers and intralesional corticosteroids injections in treatment of IHs. Patients and methods This was a prospective study that included 52 patients diagnosed with IH in two pediatric surgery tertiary centers in Egypt. Patients were divided into two groups: group A patients underwent intralesional injection of betamethasone at a dose of 10–40 mg/ml in three to six separate sessions at an interval of 1 month, whereas group B patients were given oral propranolol at a low dose of 0.5–1 mg/kg/day for 3–6 months. Changes in size and color of the hemangioma each month and the occurrence of any complications were recorded for 6 months. Regression of size was classified into excellent (75–100% decrease in size), good (50–75% decrease), poor (25–50% decrease), and no response. Results ‘Good’ response to intralesional corticosteroids was achieved in nine patients, whereas most patients had either ‘poor’ or ‘no response’ (n=14). On the contrary, most patients in the propranolol group exhibited ‘excellent’ or ‘good’ response (n=21) with only four patients not responding to treatment. Ulceration occurred in two patients who underwent intralesional steroid injection, whereas hypotension occurred in one patient with B-blockers. Conclusion Our study confirms the superiority of oral B-blockers in treatment of superficial IH when compared with intralesional injection of steroids.

Flexible liposomal gel dual-loaded with all-trans retinoic acid and betamethasone for enhanced therapeutic efficiency of psoriasis

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT.ResultsFlexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis.ConclusionsFlexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

Quantitative Prediction of the Role of Placental Efflux to Optimize Dosing Regimens of Dexamethasone and Betamethasone to Prevent Respiratory Distress Syndrome

IntroductionRespiratory distress syndrome is one of the major causes of newborn deaths. Dexamethasone (DEX) and Betamethasone (BET) may promote fetal lung maturation when administered to pregnant women at risk of preterm birth. Usually, DEX‐phosphate (6 mg) is administered IM q 12 hrs over 48 hrs while BET is administered IM as a 50:50 phosphate and acetate combination (12 mg total) q 24 hrs over 48 hrs. Recent non‐clinical trials suggest lower concentration would result in effective treatment for these drugs. In sheep, fetal BET plasma concentrations >1 ng/mL appears to adequately promote fetal lung maturation. Therefore, there is a need to optimize the dosing regimen of these drugs. DEX and BET are substrates of P‐gp, a placental efflux transporter, that can reduce their fetal plasma concentrations. We have recently developed a maternal‐fetal PBPK model to predict maternal‐fetal plasma concentrations of drugs throughout pregnancy. The model has been populated with physiological changes observed in pregnancy including that in hepatic activity of CYP enzymes. Using this model, our aims were to 1) predict maternal plasma concentration‐time profiles of DEX and BET, after IM administration, and compare them with those observed; 2) determine the extent of placental P‐gp activity necessary to match the predicted and observed fetal DEX/BET plasma concentrations; 3) use these data to design maternal dosing regimens of DEX and BET that minimize maternal plasma concentrations while maintaining fetal plasma concentrations > 1 ng/ml.MethodNon‐pregnant PBPK model for both drugs was developed in SimCYP where hepatic intrinsic clearance by CYP3A (CLhep,int), renal clearance and absorption rate constants of IM DEX and BET, were optimized based on literature data. A single first‐order absorption rate was used for IM DEX‐phosphate. Distinct absorption rate constants were used for IM BET‐phosphate and IM BET‐acetate. The maternal PBPK model was developed in MATLAB Simulink and populated with maternal gestational age‐dependent changes as well as placental passive diffusion and fetal hepatic clearance of the drugs. Theoretical DEX and BET fetal plasma concentration‐time profiles were simulated with varying magnitudes of P‐gp efflux until their predicted fetal plasma concentration‐time profiles adequately encompassed the observed data and the fetal PK parameters (AUC and Cmax) fell within 0.8 to 1.25‐fold of observed values.Results and DiscussionBoth non‐pregnant and pregnancy PBPK models for DEX were verified with the observed data. The pregnancy model for BET (i.e CLhep, int) needed to be optimized to describe the observed maternal plasma concentration data. Sensitivity analysis showed that the fraction of DEX and BET transported by placental P‐gp needed to be 0.6 and 0.5, respectively, to best describe the observed fetal plasma concentration data. Using these data, we are devising dosing regimens of DEX and BET for pregnant women that have the potential to maximize their efficacy and minimize their toxicity. These dosing regimens will be presented.Support or Funding InformationThis work is Supported by Bill & Melinda Gates Foundation grant OPP1190468

Coupling of liquid-liquid extraction and mathematical filtration techniques for the separation and quantification of five components in semisolid dosage form with severely overlapped spectra.

Quadriderm cream was a combination of four components; Clioquinol (CLIO), Betamethasone (BETA), Tolnaftate (TOL), Gentamicin (GEN) in addition to the preservative Chlorocresol (CC). Four components CLIO, TOL, BETA, and CC were extracted in methanol and determined by mathematic filtration spectrophotometric techniques. The partially overlapped spectrum of CLIO was determined by constant value, constant multiplication, and concentration value methods then eliminated via spectrum subtraction (SS) to get the resolved ternary mixture of TOL, BETA, and CC with severely overlapping spectra. TOL was determined by derivative ratio at zero crossing point of BETA using CC as a divisor. While, BETA could be determined using TOL as a divisor at zero crossing of CC. BETA and CC were obtained using novel (DD1FS) followed by SS. By applying these novel procedures, the DD1 spectrum of each component alone was recovered where Pmax-min was directly proportional to its concentration. Liquid-liquid extraction technique was used for the semisolid dosage form where GEN was extracted with a mixture of chloroform: water (50:50, v/v); and the induced fluorescence obtained by derivatization with o-phthalaldehyde was measured at 419nm after excitation at 359nm. Accuracy and precision testing of the developed methods showed good results. Specificity of the methods was ensured and was successfully applied for the analysis of pharmaceutical formulation of the five components in combination. ICH guidelines were used for validation of the proposed methods. Statistical data were calculated, and the results were satisfactory revealing no significant difference regarding accuracy and precision.

Glycemia after Betamethasone in Pregnant Women without Diabetes-Impact of Marginal Values in the 75-g OGTT.

Betamethasone (BM) administration in pregnancy has been shown to reduce the incidence and severity of neonatal respiratory distress syndrome. Its known diabetogenic impact, combined with placental insulin resistance, leads to a transient increase in glycemia. However, its effect on glucose homeostasis in pregnancy has not been adequately investigated. We closely monitored and assessed the glycemic profile of 83 pregnant women, with normal glucose metabolism, who were given BM during their hospitalization due to threatened premature labor. A significant change in the glycemic profile in most patients was noted, lasting 1.34 ± 1.05 days. Sixty-six of eighty-three women were eventually treated with insulin to maintain glycemia within acceptable limits. The mean ± SD insulin dosage was 12.25 ± 11.28 units/day. The need for insulin therapy was associated with higher BM doses and the presence of marginal values in the 75-g oral glucose tolerance test (OGTT) at 60 min. Our study demonstrates, following BM administration, the need for increased awareness and individualized monitoring/treatment of pregnant women with normal—yet marginal—values in the 75-g OGTT.