Brozopentyl Sodium (BZP), a novel agent for ischemic stroke, has shown promising results in preclinical pharmacological studies, prompting the initiation of the first-in-human investigation.This study aimed to assess the safety, tolerability, and pharmacokinetic (PK) characteristics of BZP in Chinese healthy volunteers.The study consisted of two parts. Part I was a single-center, randomized, single-blinded, placebo-controlled, single-ascending study with six BZP dose cohorts (SAD: 25, 50, 100, 200, 300, and 400 mg). Part II was a single-center, randomized, single-blinded, placebo-controlled, multi-dose- and dose-elevated study with three BZP dose cohorts (MAD: 50, 100, and 200 mg). Doses were administered once daily on days 1 and 7 and twice daily on days 2-6. The PK properties of BZP and its bioactive metabolites, BNBP, were assessed. Safety and tolerability evaluations were also conducted.In the SAD study, BZP reached peak plasma concentrations (Tmax) at the end of administration, with median Tmax values ranging from 1 to 1.03 h, while BNBP reached Tmax between 1.25 to 1.38 h. The terminal half-lives (T1/2) were approximately 8 h for BZP and 15 h for BNBP. In the MAD study, steady-state plasma concentrations of BZP were reached by day 5. There was minimal accumulation of both BZP and BNBP after 7 days of administration. The area under the plasma concentration-time curve from 0 to time of the last measurable concentration (AUC0-t) and maximum plasma drug concentration (Cmax) showed dose-proportional increases for BZP but not for BNBP in both study parts. Single and multiple doses of BZP demonstrated a good safety profile and were well-tolerated.BZP displayed safety, good tolerability and predictable PK characteristics following both single and multiple ascending intravenous administrations. These findings provide a basis for further clinical development of BZP for ischemic stroke patients.
Abstract The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once‐daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1 hour (median). Plasma concentrations declined rapidly following the attainment of peak concentrations, with a mean terminal half‐life of 5.7 to 7.3 hours. Steady‐state plasma concentrations of baricitinib were achieved after the second day of once‐daily dosing, with minimal accumulation of baricitinib in plasma (up to 10% increase in area under the plasma concentration–time curve). Single‐ and multiple‐dose mean values for area under the plasma concentration–time curve from time zero to infinity and maximum plasma concentration appeared to increase in an approximately dose‐proportional manner across the dose range. Single and multiple oral doses of once‐daily baricitinib up to 10 mg were well tolerated by healthy Chinese subjects.
Abstract Background: Shende’an tablet (SDA) is a newly capsuled Chinese herbal formula derived from the Chinese traditional medicine Zhengan Xifeng Decoction which is approved for the treatment of neurasthenia and insomnia in China. This study aimed to investigate the neuroprotective effects of SDA against Parkinson’s disease (PD) in vitro and in vivo. Methods: In the present work, the neuroprotective effects and mechanism of SDA were evaluated in the cellular PD model. Male C57BL/6J mice were subject to a partial MPTP lesion alongside treatment with SDA. Behavioural test and tyrosine-hydroxylase immunohistochemistry were used to evaluate nigrostriatal tract integrity. HPLC analysis and Western blotting were used to assess the effect of SDA on dopamine metabolism and the expression of HO-1, PGC-1α and Nrf2, respectively. Results: Our results demonstrated that SDA had neuroprotective effect in dopaminergic PC12 cells with 6-OHDA lesion. It had also displayed efficient dopaminergic neuronal protection and motor behavior alleviation properties in MPTP-induced PD mice. In the PC12 cells and MPTP-induced Parkinson’s disease animal models, SDA was highly efficacious in α-synuclein clearance associated with the activation of PGC-1α/Nrf2 signal pathway. Conclusion: SDA demonstrated potential as a future therapeutic modality in PD through protecting dopamine neurons and alleviating the motor symptoms, mediated by the activation of PGC-1α/Nrf2 signal pathway.
Compound8eprotected against the collagen and adrenaline induced thrombosis in mice, and exhibited greater antithrombotic activity than NBP and aspirin in rats.
To determine the pharmacokinetics (PK) of vancomycin in Chinese infant patients using a population pharmacokinetic (PKK) approach in order to provide support for individualized vancomycin therapy.The data included 72 sets of steady-state peak and trough serum concentrations from 61 infants (0 - 1 years). PPK analysis was performed using the nonlinear mixed-effects modeling software. Inter- and intraindividual variability was estimated for the clearance and distribution volume of vancomycin. The potential effects of patient sex, postnatal age, postconceptional age, height, weight, body surface area, body mass index, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, white blood cell count, serum creatinine, and concomitant medications on vancomycin PKs were explored.A one-compartment linear model with first-order elimination was used to describe the data. Weight and postnatal age had a significant influence on vancomycin clearance. The typical population parameter estimates of clearance and distribution volume were 0.46 L/h and 4.45 L, respectively. Goodness-of-fit plots and bootstrap outcomes confirmed the relatively good stability and prediction capability of the model.This study initially established a vancomycin PPK model to estimate individual PK parameters in Chinese infant patients. .
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