Analytical Similarity Assessment of ABP 959 in Comparison with Eculizumab Reference Product

Introduction: Biosimilars present a considerable potential to reduce costs related to clinical management allowing health-care providers to reinvest this money, leading to a wider access to an effective biological treatment with monoclonal antibodies (mAb). Infliximab biosimilars have already been incorporated in daily clinical practice and are currently used in all indications for which the reference product (RP) was approved. Areas covered: In the next few years, also adalimumab biosimilars will become available for the treatment of inflammatory bowel disease (IBD). In fact, several of them (ABP501, BI 695501, GP2017, and SB5) have been approved by the European Medicines Agency (EMA) with the same indications of the reference product (Humira ®). Initial preclinical data proved a strong similarity between all biosimilars and the RP. Moreover, phase 3 studies in rheumatoid arthritis and psoriasis showed no differences in terms of efficacy, safety, and immunogenicity. Data on IBD patients are urgently needed. Expert opinion: Biosimilars of adalimumab showed equivalent clinical efficacy to the RP in other immunemediated diseases. However, defining the ideal patient’s profile to receive or to be switched to a biosimilar, choosing one biosimilar vs. another, or cross-switching among biosimilars, will become the next challenge in IBD.

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A Randomized Study on the Bioequivalence of Desloratadine in Healthy Chinese Subjects and the Association of Different Metabolic Phenotypes With UGT2B10 and CYP2C8 Genotypes

Current Drug Metabolism ◽

10.2174/1389200221999201027143903 ◽

2020 ◽

Vol 21 (13) ◽

pp. 1031-1039

Author(s):

Suping Niu ◽

Yan Li ◽

Wenliang Dong ◽

Lin Xia ◽

Tiantian Shen ◽

...

Keyword(s):

Reference Product ◽

Geometric Mean ◽

Randomized Study ◽

Metabolic Ratio ◽

Taqman Assay ◽

Serious Adverse Events ◽

Metabolic Phenotypes ◽

Test Product ◽

Healthy Chinese ◽

Chinese Subjects

Background: Desloratadine is a drug with a phenotypic polymorphism in metabolism and has been approved for use in many countries to treat allergic diseases. CYP2C8 and UGT2B10 are metabolic enzymes, which may be involved in the metabolism of desloratadine. Objective: This study aimed to demonstrate bioequivalence between the test product (desloratadine tablet) and the reference product AERIUS (5mg), both orally administered. And the role of UGT2B10 and CYP2C8 genotypes in healthy Chinese subjects with different Desloratadine metabolic phenotypes was examined. Methods: It was a randomized, open-label, and four-sequence, single-dose crossover study conducted on 56 healthy Chinese subjects. The pharmacokinetics (PK) and safety of the test and reference Desloratadine products were compared. UGT2B10 and CYP2C8 genotypes were determined by the TaqMan assay using genomic DNA. Multiple linear regression was applied to analyze the correlation between genotypes and the metabolic ratio. Results: The mean serum concentration-time curves of desloratadine and 3-OH-desloratadine were similar between the test product and the reference product. For the PK similarity comparison, the 90% CIs for the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ of desloratadine and 3-OH-desloratadine of test and reference product were completely within 80-125%. None of all 56 subjects had serious adverse events. Only 2 subjects were poor-metabolizers in 56 healthy subjects. There was no significant correlation between investigated genotypes of CYP2C8 and UGT2B10 and the metabolic ratio. Conclusion: The test desloratadine tablet was bioequivalent to the reference product. No direct relationship between CYP2C8 and UGT2B10 genotypes and desloratadine metabolic ratio was identified.

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Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation

Pharmaceutics ◽

10.3390/pharmaceutics13060849 ◽

2021 ◽

Vol 13 (6) ◽

pp. 849

Author(s):

Manasa Tatipalli ◽

Vijay Kumar Siripuram ◽

Tao Long ◽

Diana Shuster ◽

Galina Bernstein ◽

...

Keyword(s):

Pharmacokinetic Model ◽

Allometric Scaling ◽

Pediatric Patients ◽

Reference Product ◽

Population Pharmacokinetic ◽

Liquid Formulation ◽

Sampling Schemes ◽

Quantitative Pharmacology ◽

Using Data ◽

Drug Pharmacokinetics

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.

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Swallowing Gel for Patients with Dysphagia: A Novel Application of Chitosan

Gels ◽

10.3390/gels7030108 ◽

2021 ◽

Vol 7 (3) ◽

pp. 108

Author(s):

Tanikan Sangnim ◽

Pornsak Sriamornsak ◽

Inderbir Singh ◽

Kampanart Huanbutta

Keyword(s):

Molecular Weight ◽

Carboxymethyl Cellulose ◽

Stress Condition ◽

Reference Product ◽

The Elderly ◽

Oral Drug ◽

Disintegration Time ◽

Tablet Disintegration ◽

Tablet Dosage ◽

Chitosan Gel

Dysphagia refers to difficulty swallowing certain foods, liquids, or pills. It is common among the elderly with chronic diseases who need to take drugs for long periods. Therefore, dysphagia might reduce compliance with oral drug administration in the aging population. Many pharmaceutical companies search for new products to serve as swallowing aids. Existing products are expensive and do not suit all geriatric patients. Therefore, this study aimed to develop and investigate pill swallowing aid gels prepared from carboxymethyl cellulose and chitosan. We formulated gels by dissolving different concentrations of carboxymethyl cellulose and low or high molecular weight chitosan in solvents to find appropriate gel rheology properties. We then added several portions of glycerin as the glidant of the formulation. We found that the optimized gel formulation was 6.25% (w/w) chitosan with a molecular weight of 80–120 kDa dissolved in 1.2% acetic acid and 4% (w/w) glycerin. The developed pill swallowing gel’s rheology was pseudoplastic with a viscosity of 73.74 ± 3.20 Pa⸱s. The developed chitosan gel had enhanced flow ability; it allowed the pill to cross a 300 mm tube within 6 s, while the reference product took 3 s. Even though the reference product could carry the pill in the tube faster, the chitosan gel better covered the pill, making it more convenient to use. Finally, using a theophylline tablet as a model tablet dosage form, we assessed the gel’s effect on drug disintegration and dissolution. The chitosan gel delayed the tablet disintegration time by about 3–7 min and slightly affected the theophylline dissolution rate. Lastly, all gels were physically stable after a month of storage in the stress condition. These results show the feasibility of manufacturing a chitosan gel usable as a pill swallowing gel for patients with dysphagia.

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Study on design of Linxia brick carving products based on shape grammar

E3S Web of Conferences ◽

10.1051/e3sconf/202017902089 ◽

2020 ◽

Vol 179 ◽

pp. 02089

Author(s):

Zhang Shutao ◽

Xu Juanjuan ◽

Su Pengfei ◽

Su Jianning

Keyword(s):

Form Factor ◽

Reference Product ◽

Field Investigation ◽

Product Form ◽

Shape Grammar ◽

Single Type ◽

Initial Shape ◽

Emotional Demand ◽

Typical Form ◽

Characteristic Lines

In view of the problems such as the single type of cultural derivative products of Linxia brick carving and the weak cultural attraction, we carried out the application research of Linxia brick carving culture by using shape grammar. Firstly, we collected and combed the materials of brick carving culture in Linxia by means of literature research and field investigation. Then, we determined the target product, analyzed the product form and emotional demand, construct the reference product form database, screen the brick carving pattern through the matching of the product emotional demand, obtained the characteristic lines of the brick carving pattern by the way of the type spectrum analysis, and established the typical form factor database of brick carving; Finally, taking some lines in the typical form factor database as the initial shape, we combined them with the lines in the reference product form database. According to the shape grammar deduction rules, the scheme was generated, the best scheme was selected and further refined. Studies have shown that the use of shape grammar for product design can enhance the cultural connotation of products, promote cultural heritage, and effectively guide the design of Linxia brick carving products.

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Immunogenicity of an adalimumab biosimilar, FKB327, and its reference product in patients with rheumatoid arthritis

International Journal of Rheumatic Diseases ◽

10.1111/1756-185x.13951 ◽

2020 ◽

Vol 23 (11) ◽

pp. 1514-1525

Author(s):

Rieke Alten ◽

Colin Markland ◽

Malcolm Boyce ◽

Kazuki Kawakami ◽

Rafael Muniz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Reference Product

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