betamethasone-acetate and betamethasone-sodium-phosphate

To the date, no reports exist of the pharmacokinetics (PK) of betamethasone (BTM) sodium phosphate and betamethasone acetate administered intra-articular (IA) into multiple joints in exercising horses. The purpose of the study was to determine the PK of BTM and HYD concentrations in plasma and urine after IA administration of a total of 30 mg BTM. Eight 4 years old Thoroughbred mares were exercised on a treadmill and BTM was administered IA. Plasma and urine BTM and HYD were determined via high performance liquid chromatography spectrometry for 6 weeks. Concentration-time profiles of BTM and HYD in plasma and urine were used to generate PK estimates for non-compartmental analyses and comparisons among times and HYD concentrations. BTM in plasma had greater Tmax (Tmax 0.8 h) vs. urine (Tmax 7.1 h). Urine BTM concentration (ng/mL) and amount (AUClast ; h × ng/mL) were greater than plasma. HYD was suppressed for at least 3 days (<1 ng/mL) for all horses. The time of last quantifiable concentration of BTM (Tlast ; hour) was not significantly different in plasma than urine. Use of highly sensitive HPLC-MS/MS assays enabled early detection and prolonged and consistent determination of BTM in plasma and urine.

Topics: Animals; Area Under Curve; Betamethasone; Female; Glucocorticoids; Half-Life; Horses; Hydrocortisone; Injections, Intra-Articular; Metatarsus; Physical Conditioning, Animal; Tarsus, Animal

Treatment of women at risk for preterm birth with repeat doses of glucocorticoids reduces neonatal morbidity but could have adverse long-term effects on cardiometabolic health in offspring. We assessed whether exposure to repeat antenatal betamethasone increased risk factors for later cardiometabolic disease in children whose mothers participated in the Australasian Collaborative Trial of Repeat Doses of Corticosteroids.. Women were randomized to betamethasone or placebo treatment, ≥ 7 days after an initial course of glucocorticoids, repeated each week that they remained at risk for preterm birth at <32 weeks' gestation. In this follow-up study, children were assessed at 6 to 8 years' corrected age for body composition, insulin sensitivity, ambulatory blood pressure, and renal function.. Of 320 eligible childhood survivors, 258 were studied (81%; 123 repeat betamethasone group; 135 placebo [single course] group). Children exposed to repeat antenatal betamethasone and those exposed to placebo had similar total fat mass (geometric mean ratio 0.98, 95% confidence interval [CI] 0.78 to 1.23), minimal model insulin sensitivity (geometric mean ratio 0.89, 95% CI 0.74 to 1.08), 24-hour ambulatory blood pressure (mean difference systolic 0 mm Hg, 95% CI -2 to 2; diastolic 0 mm Hg, 95% CI -1 to 1), and estimated glomerular filtration rate (mean difference 1.2 mL/min/1.73 m(2), 95% CI -3.2 to 5.6).. Exposure to repeat doses of antenatal betamethasone compared with a single course of glucocorticoids does not increase risk factors for cardiometabolic disease at early school age.

Topics: Adipose Tissue; Betamethasone; Blood Pressure; Cardiovascular Diseases; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Injections, Intramuscular; Insulin Resistance; Longitudinal Studies; Male; Obstetric Labor, Premature; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors

For impurity profiling of betamethasone acetate and betamethasone phosphate injectable suspensions, a quick, verified stability indicating UPLC technique incorporating the detectors PDA-QDa had been established. This method with an analysis time of 12min could able to separate all possible degradation impurities. Two of the thermal impurities have been identified in positive mode of detection by using QDa detector and isolated by using preparative HPLC. The method works at a flow rate of 0.5mL/min in column: Poroshell 120 EC C18 (100×2.1)mm, 1.9μm, maintained temperature precisely at 40°C. The M/Z values in ESI positive mode for the two new degradation impurities have been identified (M+H) as 393.22 (DP1), 363.17 (DP2) and confirmed by

Topics: Betamethasone; Chromatography, High Pressure Liquid; Drug Contamination; Drug Stability; Phosphates; Suspensions

Antenatal corticosteroid therapy is a standard of care for women at imminent risk of preterm labor. However, the optimal (maximum benefit and minimal risk of side effects) antenatal corticosteroid dosing strategy remains unclear. Although conveying overall benefit when given to the right patient at the right time, antenatal corticosteroid treatment efficacy is highly variable and is not risk-free. Building on earlier findings, we hypothesized that when administered in combination with slow-release betamethasone acetate, betamethasone phosphate and the high maternal-fetal betamethasone concentrations it generates are redundant for fetal lung maturation.. Using an established sheep model of prematurity and postnatal ventilation of the preterm lamb, we aimed to compare the pharmacodynamic effects of low-dosage treatment with betamethasone acetate only against a standard dosage of betamethasone phosphate and betamethasone acetate as recommended by the American College of Obstetricians and Gynecologists for women at risk of imminent preterm delivery between 24 0/7 and 35 6/7 weeks' gestation.. Ewes carrying a single fetus at 122±1 days' gestation (term=150 days) were randomized to receive either (1) maternal intramuscular injections of sterile saline (the saline negative control group, n=12), (2) 2 maternal intramuscular injections of 0.25 mg/kg betamethasone phosphate+betamethasone acetate administered at 24-hour dosing intervals (the betamethasone phosphate+betamethasone acetate group, n=12); or (3) 2 maternal intramuscular injections of 0.125 mg/kg betamethasone acetate administered at 24-hour dosing intervals (the betamethasone acetate group, n=11). The fetuses were surgically delivered 48 hours after treatment initiation and ventilated for 30 minutes to determine functional lung maturation. The fetuses were euthanized after ventilation, and the lungs were collected for analysis using quantitative polymerase chain reaction and Western blot assays. Fetal plasma adrenocorticotropic hormone levels were measured in the cord blood samples taken at delivery.. Preterm lambs were defined as either antenatal corticosteroid treatment responders or nonresponders using an arbitrary cutoff, being a PaCO. Low-dosage antenatal corticosteroid therapy solely employing betamethasone acetate was sufficient for fetal lung maturation. The elevated maternal-fetal betamethasone concentrations associated with the coadministration of betamethasone phosphate did not in addition improve lung maturation but were associated with greater fetal hypothalamic-pituitary-adrenal axis suppression, a lower antenatal corticosteroid treatment response rate, and lower birthweight-outcomes not desirable in a clinical setting. These data warranted a clinical investigation of sustained low-dosage antenatal corticosteroid treatments that avoid high maternal-fetal betamethasone exposures.

Topics: Animals; Betamethasone; Birth Weight; Female; Glucocorticoids; Hypothalamo-Hypophyseal System; Lung; Pituitary-Adrenal System; Pregnancy; Sheep

Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women > 27 weeks' gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood, and amniotic fluid betamethasone time-courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood, and 26 amniotic fluid samples were described by a two-compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70 kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal-to-mother exposure ratio, the median (95% confidence interval (CI)) transplacental transfer of betamethasone was estimated to 35% (95% CI 0.11-0.67). After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent in utero below quantifiable concentrations (i.e., < 1 ng/mL): odds ratio of 1.10 (95% CI 1.01-1.19) per day increase (P < 0.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1 ng/mL without exceeding the total standard dose.

Topics: Adolescent; Adult; Amniotic Fluid; ATP Binding Cassette Transporter, Subfamily B; Betamethasone; Drug Dosage Calculations; Drug Monitoring; Female; Fetal Blood; France; Gestational Age; Glucocorticoids; Humans; Infant, Newborn; Injections, Intramuscular; Male; Maternal-Fetal Exchange; Models, Biological; Pharmacogenetics; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Pregnancy; Prospective Studies; Respiratory Distress Syndrome, Newborn; Young Adult

Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. Antenatal corticosteroid dosing remains nonoptimized, and there is little understanding of how different treatment-to-delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with antenatal corticosteroids do not deliver within the widely accepted 1- to 7-day window of treatment efficacy.. We used a sheep model to test the duration of fetal exposures for efficacy at delivery intervals from 1 to 10 days.. For infusion studies, ewes with single fetuses were randomized to receive an intravenous bolus and maintenance infusion of betamethasone phosphate to target 1-4 ng/mL fetal plasma betamethasone for 36 hours, with delivery at 2, 4 ,or 7 days posttreatment or sterile saline solution as control. Animals receiving the clinical treatment were randomised to receive either a single injection of 0.25 mg/kg with a 1:1 mixture of betamethasone phosphate + betamethasone acetate with delivery at either 1 or 7 days posttreatment, or 2 treatments of 0.25 mg/kg betamethasone phosphate + betamethasone acetate spaced at 24 hours (giving ∼48 hours of fetal steroid exposure) with delivery at 2, 5, 7, or 10 days posttreatment. Negative control animals were treated with saline solution. All lambs were delivered at 121 ± 3 days gestational age and ventilated for 30 minutes to assess lung function.. Preterm lambs delivered at 1 or 2 days post-antenatal corticosteroid treatment had significant improvements in lung maturation for both intravenous and single-dose intramuscular treatments. After 2 days, the efficacy of 36-hour betamethasone phosphate infusions was lost. The single dose of 1:1 betamethasone phosphate + betamethasone acetate also was ineffective at 7 days. In contrast, animals treated with 2 doses had significant improvements in lung maturation at 2, 5, and 7 days, with treatment efficacy reduced by 10 days.. In preterm lambs, the durability of antenatal corticosteroids treatment depends on the duration of fetal exposure and is independent of the intravenous or intramuscular maternal route of administration. For acute 24- to 48-hour posttreatment deliveries, a 24-hour fetal antenatal corticosteroids exposure was sufficient for lung maturation. A fetal exposure duration of at least 48 hours was necessary to maintain long-term treatment durability. A single-dose ACS treatment should be sufficient for women delivering within <48 hours of antenatal corticosteroids treatment.

Topics: Animals; Betamethasone; Delivery, Obstetric; Fetal Organ Maturity; Fetus; Gestational Age; Glucocorticoids; Infusions, Intravenous; Injections, Intramuscular; Lung; Prenatal Care; Sheep; Time Factors

Antenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.. The purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.. Groups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.. All betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance, gas exchange, and ventilation efficiency similarly to the standard treatment of 2 doses of 0.25 m/kg of betamethasone-acetate+betamethasone-phosphate. Betamethasone-acetate 0.125 mg/kg resulted in lower maternal and fetal peak plasma concentrations and decreased fetal exposure to betamethasone compared with betamethasone-phosphate 0.125 mg/kg.. A single dose of betamethasone-acetate results in similar fetal lung maturation as the 2-dose clinical formulation of betamethasone-phosphate+betamethasone-acetate with decreased fetal exposure to betamethasone. A lower dose of betamethasone-acetate may be an effective alternative to induce fetal lung maturation with less risk to the fetus.

Topics: Animals; Aquaporin 5; ATP Binding Cassette Transporter, Subfamily A; Betamethasone; Dose-Response Relationship, Drug; Female; Fetal Organ Maturity; Glucocorticoids; Lung; Models, Animal; Pregnancy; Pulmonary Surfactant-Associated Proteins; RNA, Messenger; Sheep

Intra-articular corticosteroid injection (IACI) of betamethasone depot preparation is a popular procedure at the knee joint. Intra-articular corticosteroid injection in general could be associated with systemic effects including suppression of the hypothalamic-pituitary-adrenal axis. There are nearly no reports on the effect of IACI of betamethasone at the knee joint on the hypothalamic-pituitary-adrenal axis.. Consecutive patients attending the rheumatology or orthopedic clinic with osteoarthritic knee pain who were not responding satisfactorily to medical and physical therapy were allocated to group 1 after consent and given IACI of 6 mg of betamethasone acetate/betamethasone sodium phosphate. After completion of this part, consecutive age- and sex-matched patients were allocated to group 2 and given intra-articular injection of 60 mg of sodium hyaluronate. Demographic, clinical, laboratory, and radiographic variables were documented. Just before the knee injection and 1, 2, 3, 4, and 8 weeks later, patients had 1-μg adrenocorticotropin hormone (ACTH) stimulation test. Secondary adrenal insufficiency (SAI) was defined as levels of less than 18 µg/dL and lack of a rise of more than 6 µg/dL in serum cortisol level, 30 minutes after the ACTH stimulation test.Patients were blinded to the injected material, and all injections were ultrasound guided.. Twenty patients were enrolled in each group and equally divided between the 2 sexes. The mean age of the patients was approximately 54 years in both groups. No significant difference in any variable was seen between the 2 groups. One patient only from group 1 (the betamethasone group) had SAI 3 weeks after the IACI compared to none in the control group (P > 0.9999). His serum cortisol level 30 minutes after the ACTH stimulation was 17 µg/dL, with a rise of 3 µg/dL from baseline.. Intra-articular corticosteroid injection of 6 mg of betamethasone acetate/betamethasone sodium phosphate at the knee joint was not significantly associated with SAI at the time points tested.

Topics: Adult; Aged; Betamethasone; Case-Control Studies; Female; Humans; Hypothalamo-Hypophyseal System; Injections, Intra-Articular; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pituitary-Adrenal System; Treatment Outcome