Efficacy of Yigu® versus Aclasta® in Chinese postmenopausal women with osteoporosis: a multicenter prospective study

Summary Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

A Comparative Pharmacokinetic Study to Evaluate the Bioequivalence and Safety of A Humanized Recombinant Monoclonal Antibody Targeting Human Epidermal Growth Factor Receptor 2 (HER2) with the Reference Herceptin in Healthy Chinese Subjects

Purpose:This study aimed to evaluate the safety, tolerability, pharmacokinetics and bioequivalence of a test humanized recombinant monoclonal antibody targeting Human Epidermal Growth Factor receptor 2 (HER-2) with the reference Herceptin®.Materials and methods:The trial consists of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, QLHER2 (test) was intravenous infusion at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4 and 6mg/kg) and Herceptin(reference) 4 mg/kg in 16 healthy subjects, to evaluated the safety, tolerability and pharmacokinetics of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.Results:Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) In part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h*μg/mL and 0.54-0.12 ml/h/kg, indicating decreased clearance at higher doses, with a greater than proportional increase in the AUC0-t , and the t1/2 was 68.91-157.87 h. In part II, Plasma concentrations appeared to be comparable between QLHER2 and Herceptin over the 70-day sampling period and the QLHER2/Herceptin ratio of the Cmax and AUC0-t was 105.90% (90% CI: 95.69-117.26) and 95.79% (90% CI: 87.74-106.40%), respectively.Conclusion:The 90% CIs of the Cmax and AUC0-t for QLHER2/Herceptin ratio were within the range of 80.0-125.00% indicated that QLHER2 was bioequivalent to Herceptin. The results supported for further evaluation of QLHER2.Trial registration number: ChiCTR2000041577 and ChiCTR2100041802Date of registration: December 30,2020 and January 5, 2021

Clinical Pharmacology of Rocuronium in Infants and Children

The main clinical use of the neuromuscular blocking agents is an adjuvant in surgical anaesthesia to obtain relaxation of skeletal muscle, particularly of the abdominal wall, to facilitate surgical manipulations. Rocuronium can be used instead of suxamethonium to provide rapid muscle paralysis during tracheal intubation but the recovery is much slower. Rocuronium is administered intravenously to infants and children. In infants, rocuronium is administered at a dose of 450 µg/kg for providing muscle relaxation for laryngeal intubation. To provide sustained paralysis, rocuronium is given at a dose of 600 µg/kg. In children, the neuromuscular blockade is obtained with 600 µg/kg followed by an intravenous infusion of 150 µg/kg per hour. For assisted ventilation in intensive care, rocuronium is administered at a dose of 600 µg/kg followed by an intravenous infusion of 300 to 600 µg/kg per hour. The effects of rocuronium have been extensively studied in infants and children. Rocuronium is converted into 17-desacetyl rocuronium. The pharmacokinetics of rocuronium have been studied in infants and children and the mean residence time is 55.6 and 25.6 min (P-value < 0.01) in infant and children, respectively. Rocuronium interacts with drugs, the treatment of infants and children with rocuronium has been studied, and rocuronium poorly crosses the human placenta. The aim of this study is to review the published data on rocuronium dosing, pharmacokinetics, and treatment in infants and children, and rocuronium metabolism and transfer across the human placenta.

Efficacy of prophylactic tranexamic acid administration in prevention of postpartum hemorrhage in placenta previa cesarean section: an interventional study

Background: Postpartum hemorrhage accounts for the major part of the mortality as well as morbidity like severe anemia, need for blood transfusion, hospital stay and infection. Aim and objectives of the study were to determine the efficacy and safety of prophylactic tranexamic acid and intravenous tranexamic acid in preventing postpartum hemorrhage in women undergoing caesarean section for placenta previa.Methods: Seventy women with placenta previa over 1 year, randomized into 2 groups: group 1 (n=35): Women who received 10 IU oxytocin intravenous infusion after placental delivery and group 2 (n=35): Women who received 1 gm (10 ml) tranexamic acid IV before skin incision plus 10 IU oxytocin intravenous infusion after placental delivery.Results: The mean age was similar in 2 groups i.e., 26.34±4.78 years in group 1 and 27.31±5.62 years in group 2. Most women in the present study presented with type IV placenta previa i.e., 34.3% in group 1 and 48.6% in group 2. Mean pre-operative hemoglobin was 9.57±1.54 g/dl in group 1 and 9.59±1.35 g/dl in group 2. Intra-operative mean blood loss was 729.31±172.45 ml in intravenous oxytocin group and 464.86±28.00 ml in intravenous tranexamic acid group. A total of 74.3% women in group 1 and 20% women in group 2 developed postpartum hemorrhage. Mean post-operative hemoglobin was 8.04±1.34 g/dl in group 1 and 8.85±1.26 g/dl in group 2. In group 1, 5.7% neonates were born with very low birth weight and while none in group 2. 51.4% neonates in group 1 and 45.7% in group 2 had low birth weight.Conclusions: It is concluded that tranexamic acid used prophylactically intravenously before skin incision in patients undergoing cesarean section for placenta previa significantly reduces intra-operative blood loss.

Development of a Bamlanivimab Infusion Process in the Emergency Department for Outpatient COVID-19 Patients

The coronavirus disease 2019 (COVID-19) pandemic has prompted the creation of new therapies to help fight against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Bamlanivimab is a SARS-CoV-2 monoclonal antibody that is administered as an intravenous infusion to ambulatory patients with mild or moderate COVID-19, but a concern that arose was deciding the optimal location for patients to receive the medication. This report describes the development and implementation of a bamlanivimab infusion center in the emergency department of three hospitals in Orange County, California, shortly after bamlanivimab received emergency use authorization. As a result, a total of 601 patients received bamlanivimab in one of these three emergency departments between December 2020 to April 2021. The emergency department was shown to be an optimal setting for administration of bamlanivimab due to its convenience, accessibility, and capabilities for monitoring patients.

Intravenous infusion route in maternal resuscitation: a scoping review

Background The concept that upper extremities can be used as an infusion route during cardiopulmonary resuscitation in pregnant women is a reasonable recommendation considering the characteristic circulation of pregnant women; however, this method is not based on scientific evidence. Objective of the review We conducted a scoping review to determine whether the infusion route should be established above the diaphragm during cardiopulmonary resuscitation in a pregnant woman. Discussion We included randomized controlled trials (RCTs) and non-RCTs on the infusion of fluids in pregnant women after 20 weeks of gestation requiring establishment of an infusion route due to cardiac arrest, massive bleeding, intra-abdominal bleeding, cesarean section, severe infection, or thrombosis. In total, 3150 articles from electronic database were extracted, respectively. After title and abstract review, 265 articles were extracted, and 116 articles were extracted by full-text screening, which were included in the final analysis. The 116 articles included 78 studies on infusion for pregnant women. The location of the intravenous infusion route could be confirmed in only 17 studies, all of which used the upper extremity to secure the venous route. Conclusion Pregnant women undergo significant physiological changes that differ from those of normal adults, because of pressure and drainage of the inferior vena cava and pelvic veins by the enlarged uterus. Therefore, despite a lack of evidence, it seems logical to secure the infusion route above the diaphragm when resuscitating a pregnant woman.