Yan Liang’s research while affiliated with Beijing Medical University and other places

Remimazolam is a new ultra-short-acting benzodiazepine used to induce and maintain anesthesia and procedural sedation. Its compound structure is similar to midazolam's. Midazolam metabolism might be affected by vitamin D receptor (VDR), cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms. This study investigated the effects of VDR, cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms on the pharmacokinetics of remimazolam in healthy Chinese volunteers after a single intravenous injection of remimazolam besylate. Blood samples were collected from subjects (n = 62) at scheduled time intervals before and after injection. High-performance liquid chromatography-tandem mass spectrometry was used to quantify plasma remimazolam and RF7054 (its inactive carboxylic acid metabolite) concentrations. The relationship between plasma remimazolam concentration, pharmacokinetic parameters, and polymorphic alleles was assessed for each subject. The rs4516035 allele affected the elimination half-life of RF7054 (P = .043), while the rs1544410 allele affected the dose-normalized maximum observed plasma concentration (Cmax /D) of remimazolam (P = .025) in 46 volunteers. Results showed that VDR genetic polymorphisms might affect the pharmacokinetics of remimazolam in the Chinese population.

Purpose: The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous infusion in healthy Chinese volunteers. Methods: This was a randomized phase I study conducted in two parts. Part I was a double-blind, placebo- and midazolam-controlled, SAD study among healthy Chinese participants with a remimazolam dose of 0.025-0.4 mg/kg. Part II was an open-label, midazolam-controlled, continuous infusion study. Bispectral index (BIS) monitoring and Modified Observers Assessment of Alertness and Sedation (MOAA/S) score assessment were used to assess the PD properties. Results: The half-life range of remimazolam was from 34.1 ± 8.1 to 59.8 ± 20.5 min in the SAD study. The sedation function was initially observed at the dose of 0.05 mg/kg remimazolam. Doses of ≥ 0.075 mg/kg exerted a peak sedation effect within 1-2 min after injection, resulting in a deeper and more rapid sedation. In the 2 h continuous infusion, remimazolam showed a deeper sedation and more rapid recovery than midazolam. For general anesthesia, an induction dosage of 0.2 mg/kg/min and a maintenance dosage of 1 mg/kg/h can achieve a satisfactory efficacy effect. Conclusions: Remimazolam was safe and well tolerated in healthy Chinese participants. Based on the phase I clinical study, we suggest that remimazolam besylate demonstrates greater sedation and quicker recovery from sedation than midazolam.

Background: Hemoporfin is a porphyrin-based photosensitizer and has been used for photodynamic therapy of port wine stain birthmarks in China. This study assessed the pharmacokinetics and cutaneous photosensitization of Hemoporfin in healthy volunteers. Methods: Sixteen healthy subjects received a single intravenous infusion injection of Hemoporfin (5 mg/kg). The concentrations of Hemoporfin (MHD) and its metabolite Haematoporphyrin (HP) in plasma, urine and faeces were determined. The pharmacokinetic parameters were calculated. In addition, the cutaneous photosensitization was evaluated under the irradiation of solar simulator, 532 nm laser, and sunlight. Results: The Cmax of MHD and HP were 46.7 ± 8.41 and 1.04 ± 0.265 μg/ml, respectively. The t1/2 of MHD and HP were 5.09 ± 0.945 and 5.71 ± 2.65 h, respectively. The AUC0-24h of MHD and HP were 29.8 ± 6.19 and 0.757 ± 0.285 h·μg/ml, respectively. The AUC0-∞ of MHD and HP were 29.8 ± 6.2 and 0.792 ± 0.308 h·μg/ml, respectively. The cumulative fecal excretion rate of MHD and HP were 45.3% and 1.05% at 96 h, respectively. Whereas, the cumulative urinary excretion rate of MHD was only 0.132% at 96 h. The concentration of HP in urine was less than 10% of MHD. After 52 h of administration, the cutaneous photosensitization associated with the exposure to various light sources was minimal. Conclusion: MHD and HP were excreted mainly through the faeces after intravenous infusion. Hemoporfin associated cutaneous photosensitization was insignificant.

Aim: Evaluate steady-state pharmacokinetics and potential interactions between select statins and evacetrapib. Patients & methods: This open-label, two-part study included 62 healthy native Chinese subjects. Part 1 evaluated pharmacokinetics and pharmacodynamics of evacetrapib after 1 or 14 once-daily doses. Part 2 evaluated pharmacokinetics and pharmacodynamics of simvastatin, atorvastatin and evacetrapib administered alone, and of statin + evacetrapib coadministered. Results: Evacetrapib estimated accumulation ratio following once-daily dosing was 2.7. Simvastatin or atorvastatin coadministration reduced evacetrapib AUC 0–24 by 12% (90% CI: -0.1 to -22%) or 10% (90% CI: -23–5%), respectively. Evacetrapib coadministration increased simvastatin or atorvastatin AUC 0–24 by 123% (90% CI: 91–159%) or 16% (90% CI: 6–27%), respectively. Evacetrapib administered alone and with a statin increased high-density lipoprotein cholesterol, decreased low-density lipoprotein cholesterol, and was well tolerated. Conclusion: The significant increase in simvastatin exposure after evacetrapib coadministration was unexpected compared with previous evacetrapib and simvastatin interaction studies.

MicroRNA-21 (miRNA-21) has recently been shown to be a promising prognostic tumor biomarker. However, few studies have not supported this idea and have shown inconsistent data. Thus, we conducted a meta-analysis to elucidate the predictive value of miRNA-21 in gliomas. The relevant studies were identified by performing online search in PubMed, EMBASE and Web of Science databases up to Apr 2016. This meta-analysis study included seven eligible studies, consisting of 1121 gliomas and 533 glioblastoma multiforme (GBM) patients. Heterogeneity between studies was assessed using Egger’s and Begg’s test. Hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS), which compared the expression levels of miRNA-21 in patients with gliomas, were extracted and estimated. Our analysis revealed that the high expression of miRNA-21 is associated with the worse OS in gliomas. Further subgroup analysis indicated that increased expression of miRNA-21 was also associated with OS in GBM patients. Moreover, we observed a correlation between miRNA-21 expression and the World Health Organization defined gliomas grading system (WHO grade). Besides, high miRNA-21 expression was significantly correlated with lowered OS both in the Asian group and non-Asian group. In the cut-off subgroup analysis, both mean cut off value and median cut off value were significantly associated with OS. The expression level of miRNA-21 was not high in low KPS (Karnofsky score) group. miRNA-21 appears to be a promising biomarker for predicting the progression of patients with gliomas or GBM. However, due to the limited sample size, further prospective or retrospective multi-center well designed studies with adequate sample size should be conducted to verify its definite prognostic value.

Development and use of better medicine for children is a worldwide problem recently, especially in China. The current situation of drugs for children's renal diseases is far from well-understood now. This survey focused on drugs for pediatric renal diseases including immunosuppressants, corticosteroids, diuretics, anticoagulants, hypotensives and antilipemic agents.Information regarding the dosage, form, precaution, usage and administration in inserts was collected in this study. Drugs for pediatric renal diseases were selected according to the guidelines established by the Chinese Society of Pediatric Nephrology. The detailed information about the dosage, form of drugs was searched on the website of China-State Food and Drug (SFDA). The information of the precaution, usage and administration was obtained from the China Pharmaceutical Reference, the first edition. In this study, there were 5 categories of medicine including immunosuppressants, corticosteroids, diuretics, anticoagulants, hypotensives and antilipemic agents, and 89 kinds of medicine for renal diseases. Among these medicines, 65.2% were found not suitable for children in terms of drug dosage and form, 19.1% did not indicate the precaution, 51.7% did not indicate clearly the safety and effectiveness for children, and 56.2% lacked the detailed information about the usage and administration for children. There were only 4 kinds of these medicines which were studied via clinical trials in children population. There is a lack of drugs for children with renal diseases. Most of the time, the medicines used by doctors are not specially manufactured for children. The safety and efficacy of drugs that are currently used to treat pediatric renal diseases are not clear and definite.In addition, few clinical trials have been conducted for evaluation of drugs for pediatric renal diseases.In clinic, the situation of off-label drug treatment is very serious.

The objectives of the present study were to investigate the pharmacokinetics (PK) of tacrine analogue octahydrogenacridine (OHA) succinate tablets in healthy Chinese subjects. A single-center, randomized, open-label, dose-escalation study was conducted in 42 healthy Chinese subjects. Part I of the study (n=30, 16 male and 14 female) evaluated the PK profiles of OHA in healthy Chinese subjects (aged 18-45 years) after single and multiple doses of 2 mg, 4 mg and 8 mg. Part II (n=10) assessed food effect on PK characteristics of OHA. The 10 participants of 4 mg dose group in part I were given another single dose of 4 mg OHA under fed condition. Part III (n=12, 7 male and 5 female) investigate PK behavior of OHA in elderly (aged 65-75 years) Chinese healthy subjects. In Part I, following a single- and multiple-dose, octahydrogenacridine succinate was rapidly absorbed with a median t(max) of 0.67 to 1.00 h, and was eliminated with a mean t(1/2) of 2.27 to 2.98 h in all dose groups and did not appear to be dose dependent. In Part II, there were no significant differences in C(max), AUC(0-tn) or t(max) between 4 mg single dose fasting group and fed group (p=0.257, 0.153, 0.098, respectively). In Part III, both in single-dose and multiple-dose treatment, the main PK parameters of OHA in the elderly healthy Chinese subjects showed no statistical difference with those of non-elderly group. All these results indicated that OHA might be a promising drug under development for Alzheimer's disease (AD) therapy.

To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain (PWS), in healthy Chinese volunteers following single-dose administration. Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin (2.5, 5, 7.5 or 10 mg/kg) via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection (HPLC/FLD) method. Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase (ALT) concentration was found in 3 subjects, and increased alkaline phosphatase (ALP) concentration in one subject. The half-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. C(max) and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%. Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period.