Current Issue : October-December Volume : 2024 Issue Number : 4 Articles : 5 Articles
Purpose: The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects. Methods: A total of 72 subjects were randomly assigned to the fasting cohort (n = 36) and fed cohort (n = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC–MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a referencescaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations. Results: For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (Cmax; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration–time curve from time 0 to the last detectable concentration (AUC0-t) and from time 0 to infinity (AUC0-∞). The geometric mean ratio (GMR) of the test/reference for Cmax was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC0-t and AUC0-∞ comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%– 103.90%) and 98.71% (93.93%–103.75%), respectively. For the fed status, the subject standard deviation values of Cmax, AUC0-t, and AUC0-∞ were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for Cmax, AUC0-t, and AUC0-∞ were 101.19% (91.64%–111.74%), 98.80% (94.47%–103.33%), and 98.63% (94.42%–103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3- hydroxydesloratadine was also within 80%–125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient. Conclusion: The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm® (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status....
Objectives: To evaluate the efficacy of biosimilar (BIO) pegfilgrastim (PEG) in lymphoma patients after autologous stem cell transplantation (ASCT). Methods: 86 consecutive lymphoma patients who received BIO/PEG after ASCT were assessed. The primary endpoints of this study were the incidence of febrile neutropenia (FN) and time to neutrophil engraftment. Results: Most patients were males (67.4%) with a median age of 48 years. FN occurred in 66 patients (76.7%), and most of the fever was grade 1-2. The median time to neutrophil engraftment was 9 days. The incidence of FN differs based on lymphoma type (p-value <0.01) and was higher in non-Hodgkin lymphoma (NHL) than in Hodgkin Lymphoma (HL). No statistical difference was found between NHL and HL regarding the time to reach the neutrophil engraftment. Hospitalization lasted from a minimum of 9 to a maximum of 34 days. The restricted mean time to discharge was 15.9 days (95%CI 14-16), without differences based on lymphoma type. Conclusion: Although the study has the significant limitation of not being randomized and not having a control arm, it highlights the efficacy and safety of a BIO-PEG formulation in patients with Lymphoma and undergoing ASCT....
Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, “dyspnea” and “headache” were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters....
The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin ®. Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin ® and MYL-1401O. In CRA, PBMC stimulated with MYL- 1401O or Herceptin ® similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin ®, strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals....
Halophytic plants possess a huge range of active constituents and medicinal benefits. In this study, extracts (water, ethanol, ethyl acetate, dichloromethane, and n-hexane) of two halophytes of the genus Petrosimonia (P. brachiata and P. nigdeensis) were investigated for their phytochemical profiles and pharmacological properties. The phytochemical profiles of both species were investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. The two species show different polyphenolic profiles and these are influenced by the different extraction solvents used. The same extracts were used for different bioactivity assays. The results show that all extracts yielded total flavonoid and phenolic contents of 11.14–24.22 mg GAE/g and 3.15–22.03 mg RE/g, respectively. While extracts of both species demonstrated a radical scavenging ability in the ABTS assay (16.12–98.02 mg TE/g), only the polar and moderately polar extracts (water, ethanol, and ethyl acetate) showed scavenging potential in the DPPH assay (4.74–16.55 mg TE/g). A reducing potential was also displayed by all extracts in the CUPRAC and FRAP assays (26.02–80.35 mg TE/g and 31.70–67.69 mg TE/g, respectively). The total antioxidant capacity of the extracts ranged from 0.24 to 2.17 mmol TE/g, and the metal chelating activity ranged from 14.74 to 33.80 mg EDTAE/g. The water extracts possessed a higher metal chelating power than the other extracts. All extracts acted as inhibitors of acetylcholinesterase (0.16–3.85 mg GALAE/g) and amylase (0.11–1.28 mmol ACAE/g). Moreover, apart from the water extracts, the other extracts also showed anti-butyrylcholinesterase activity (0.73–2.86 mg GALAE/g), as well as anti-tyrosinase (36.74–61.40 mg KAE/g) and antiglucosidase (2.37–2.73 mmol ACAE/g) potential. In general, the water extracts were found to be weak inhibitors of the tested enzymes, while the ethanol extracts mostly showed an inhibitory effect. The obtained findings revealed the antioxidant and enzyme inhibitory properties of these two species and demonstrated that the solvent type used affected the pharmacological properties of the extracts and hence, can be useful to further investigate the active constituents yielded in the extracts and understand the mechanisms involved....
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