Dataset Information

The Effect of Tanreqing Injection on the Pharmacokinetics of Sirolimus in Rats.

ABSTRACT: To evaluate the effect of Tanreqing injection on the pharmacokinetics of sirolimus in rats, a high performance liquid chromatography tandem mass spectrometry method was developed for sirolimus assay in whole blood. Calibration curve of sirolimus was acquired over a concentration ranging from 2.5 to 100?ng/mL with r²= 0.9955. The matrix effects and extraction recoveries of sirolimus ranged from 144% to 152% and from 80% to 96%, respectively. The inter- and intraday relative standard deviations were both <10%. The stability investigation showed that the blood samples were stable for 30-day-storage at -20°C, for 8?h storage at room temperature, for 24?h storage in the auto-sampler at 4°C, and for three freeze-thaw cycle process. The pharmacokinetic results demonstrated that the C _max, AUC, and AUMC of sirolimus in rats (7.5?mg/kg, i.g.) were increased after beincoadministration with Tanreqing Injection at 2.5, 5.0, and 7.5?mL/kg (i.v.), respectively, or at 5?min, 2?h, and 4?h (5.0?mL/kg, i.v.) after SRL dosing, respectively. For the first time, the results proved the herb-drug interaction between Tanreqing Injection and sirolimus and accordingly suggested avoiding concurrent reception of those two drugs for patients.

SUBMITTER: Zhang F

PROVIDER: S-EPMC6431440 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Effect of Tanreqing Injection on the Pharmacokinetics of Sirolimus in Rats.

Zhang Feng F Sun Liang L Zhai Jianxiu J Xia Tianyi T Jiang Wei W Li Mingming M Gao Shouhong S Tao Xia X Chen Wansheng W Chai Yifeng Y

BioMed research international 20190310

To evaluate the effect of Tanreqing injection on the pharmacokinetics of sirolimus in rats, a high performance liquid chromatography tandem mass spectrometry method was developed for sirolimus assay in whole blood. Calibration curve of sirolimus was acquired over a concentration ranging from 2.5 to 100 ng/mL with r<sup>2</sup>= 0.9955. The matrix effects and extraction recoveries of sirolimus ranged from 144% to 152% and from 80% to 96%, respectively. The inter- and intraday relative standard de ...[more]

PMID: 30956975

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Project description:The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex.Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses.Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively).Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.

Project description:Long-term nitroglycerin (NTG) therapy causes tolerance to its effects attributing to increased oxidative stress and endothelial dysfunction. Shenmai injection (SMI), which is clinically used to treat cardiovascular diseases, consists of two herbal medicines, Ginseng Rubra and Ophiopogonjaponicas, and is reported to have antioxidant effects. The present study was designed to investigate the potential preventive effects of Shenmai injection on development of nitroglycerin-induced tolerance. The present study involves both in vivo and in vitro experiments to investigate nitroglycerin-induced tolerance. We examined the effect of Shenmai injection on the cardiovascular oxidative stress by measuring the serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Endothelial dysfunction was determined by an endothelium-dependent vasorelaxation method in aortic rings and NOS activity. Inhibition of the cGMP/cGK-I signalling pathway was determined from released serum levels of cGMP and the protein expression levels of sGC, cGK-I, PDE1A and P-VASP by western blot. Here, we showed that SMI ameliorated the decrease in AV Peak Vel, the attenuation in the vasodilation response to nitroglycerin and endothelial dysfunction. SMI also reduced the cardiovascular oxidative stress by reducing the release of MDA and increasing the activity of SOD. Shenmai injection further ameliorated inhibition of the cGMP/cGK-I signalling pathway triggered by nitroglycerin-induced tolerance through up-regulating the protein expression of sGC, cGK-I, and P-VASP and down- regulating the proteins expression of PDE1A. In vitro studies showed that Shenmai injection could recover the attenuated vasodilation response to nitroglycerin following incubation (of aortic rings) with nitroglycerin via activating the enzymes of sGC and cGK-I. Therefore, we conclude that Shenmai injection could prevent NTG nitroglycerin-induced tolerance at least in part by decreasing the cardiovascular oxidative stress, meliorating the endothelial dysfunction and ameliorating the inhibition of the cGMP/cGK-I signalling pathway. These findings indicate the potential of Shenmai injection (SMI) as a promising medicine for preventing the development of nitroglycerin-induced tolerance.

Project description:BACKGROUND:Tanreqing injection, as a kind of traditional Chinese medicine injection widely used in clinic, has the effects of clearing heat, reducing phlegm and detoxifying, and avoids the problems of slow effect and complicated decocting of traditional Chinese medicine. Severe pneumonia is a critical disease of the respiratory system, with symptoms such as dyspnea, shortness of breath, high fever, and coma. Clinical studies have found that Tanreqing injection combined with Western medicine has a good effect in the treatment of severe pneumonia. In order to explore the efficacy and safety of Tanreqing injection combined with antibiotics in the treatment of severe pneumonia, we plan to conduct a systematic evaluation and meta-analysis. METHODS:Randomized controlled trials (RCTs) on the treatment of severe pneumonia with Tanreqing injection combined with western medicine were collected by searching PubMed, The Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, Weipu Database, and China Biomedical Literature Service System (CBM) by computer with the retrieval time from establishment of database to July 2020. Two researchers independently screened and extracted the literature, and finally evaluated the bias risk of the included study, and meta-analysis was conducted using RevMan5.3 software. RESULTS:The study evaluated the efficacy and safety of Tanreqing injection combined with Western medicine in the treatment of severe pneumonia in terms of total response rate, CURB-65 score, white blood cell count (WBC), antipyretic time (AT), adverse reaction incidence, etc. CONCLUSIONS:: This study will provide a reliable evidence-based basis for the clinical application of Tanreqing injection in the treatment of severe pneumonia. ETHICS AND DISSEMINATION:The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/SQDMG.

Dataset Information

The Effect of Tanreqing Injection on the Pharmacokinetics of Sirolimus in Rats.

Publications

The Effect of Tanreqing Injection on the Pharmacokinetics of Sirolimus in Rats.

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