PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2020
·
IF 2.169
Zhang Yong,Wang Xingqi,Huang Jie,Hu Rongfeng,Chu Xiaoqin
Objective: The purpose of this study was to study the effects of formulation of cinnamaldehyde submicron emulsion (CA-SME) and optimize the preparation process parameters of CA-SME, characterize CA-SME and study on in vitro release kinetics and in vivo pharmacokinetics.Methods: Single factor methodology was used to screen the formulation of CA-SME. Response surface methodology combined with Box–Behnken design (BBD) was used to optimize the process variables of CA-SME. The dynamic dialysis method was used to investigate the in vitro release of CA from CA-SME. The blood concentrations of CA in rats were measured after oral administration of CA-SME, with CA solution as reference.Results: The optimal formulation of CA-SME was as follows: 2.5% CA + 1.5% Tween-80 and Span-80 (1:1)+1.5% medium chain triglyceride (MCT)+1.5% Poloxamer-188 + 1.5% lecithin + 91.5% ultrapure water. With the entrapment efficiency (EE/%) of CA-SME as index, BBD experiments indicated that the optimum emulsification temperature, homogenization pressure and cycles were 56 °C, 52 MPa, and two cycles, respectively. The mean particle size and EE of optimum CA-SME were 257.23 ± 3.74 nm and 80.31 ± 0.68%, respectively. The in vitro release study exhibited that the release kinetics of CA-SME was first-order model. Pharmacokinetic parameters of CA-SME in rats were Tmax 60 min, Cmax 1063.41 mg/L, AUC0–∞ 113102.61 mg/L*min, respectively. Tmax, Cmax, and AUC0–∞ of CA-SME were 3, 3.5, and 2.3 times higher than that of CA solution, respectively. The pharmacokinetic parameters of CA-SME in rats were significantly higher than those of CA solution. Submicron emulsion shows great potential as delivery strategy for this volatile herbal oil in oral administration.
研究领域:
药剂学
·
制药技术
·
药动学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Bioanalysis
·
2025
·
IF 1.8
Kaiwei Luo,Danrui Liu,Shengshuo Zhang,Xin Zhang,Qunan Cheng,Jie Lin,Yonghua Yu
Aims This study aimed to establish a robust LC-MS/MS method for quantifying trazodone in human plasma and investigate its pharmacokinetic profile in healthy Chinese subjects under fasting and fed conditions.Materials & methods A validated LC-MS/MS method using protein precipitation was applied to analyze trazodone in 68 healthy subjects (34 fasting/34 fed), with full method validation performed.Results This method exhibited high selectivity, precision, and accuracy. The results showed good linearity in the range of 5–3000 ng/mL and matrix effect results showed no matrix interference. The pharmacokinetic data revealed notable differences between the fasting and postprandial states.Conclusions The validated LC-MS/MS method proved reliable for trazodone quantification. The observed food effects on absorption suggest clinical dosing should consider administration conditions to ensure optimal therapeutic outcomes.
研究领域:
分析化学
·
药理学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Xucong Huang,Zhenghua Wu,Yanchao Liu,Mengqi Jia,Wenjuan Zhao,Shuowen Wang,Xinhui Jiang,Yuefen Lou,Guorong Fan
A simple, sensitive, and rapid LC-MS/MS method for the simultaneous determination of BIC, the M7 and M8 active metabolites in SD rat plasma was developed. After salting-out assisted liquid–liquid extraction (SALLE) with 5 M ammonium acetate solution, the sample was analyzed on a Sciences column (C18 3.0 × 100 mm, 3 μm) using a gradient elution at 40 ℃ within 7 min. The assay displayed excellent linearity in the range of 4–2000 ng/mL for M7 and BIC, and 1–500 ng/mL for M8. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of BIC, M7 and M8 met all requirements for the quantitation in plasma samples. The pharmacokinetic result showed that the AUC (0→t) was calculated as 383.1 ± 164.4 (ng/mL·h) for BIC, and 5627 ± 1261 (ng/mL·h) for M7 after oral administration with BIC. Compared with BIC group, the pharmacokinetic parameters in BIC-NPs group were improved. Augmentation in AUC (0→t) (3.02-fold) and t 1/2 (1.43-fold) for BIC. Meanwhile, double peak phenomenon was observed on the mean plasma concentration–time curves of M7 in BIC and BIC-NPs group. In conclusion, both BIC and BIC-NPs were metabolized to abundant M7 in SD rat, which would provide a basis for researching the treatment mechanism of liver injury.
研究领域:
药物代谢
·
药理学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
XENOBIOTICA
·
2024
·
IF 1.3
Li Shao,Jiajia Mo,Qinlong Xu,Guangwei He,Chunyu Xing,Zhaoxing Chu
HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC–MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1–7.6% after transdermal application of 1–4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.
研究领域:
药理学
·
皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 5
·317-329
·
IF 2.1
Xiaocui Li,Qi Liang,Caiyan Wang,Huawei Qiu,Tingting Lin,Wentao Li,Rong Zhang,Zhongqiu Liu,Lijun Zhu
BackgroundYunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear.ObjectiveThe objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC.MethodsThe efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice.ResultsThe presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco-2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice.ConclusionYAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.
研究领域:
药理学
·
毒理学
·
中药学
✓ 已验证
DOI
PubMed
高影响因子
Current Drug Delivery
·
2021
·Vol. 18
·期 2
·224-233
·
IF 2.565
Xie Shuyu,Zhang Xiaoqiu,Luo Wanhe,Meng Kuiyu,Chen Dongmei,Pan Yuanhu,Tao Yanfei,Huang Lingli,Liu Zhenli,Wang Yulian,Yuan Zonghui
Objective: A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending agents, and surfactants. Methods: Its properties, stability, injection site irritation, in vitro
release, and pharmacokinetics in pigs were evaluated. The optimum formulation was used ethyl oleate, aluminum monosterate, and span-80 as organic solvents, suspending agents, and surfactant, respectively. The drug microparticles were uniform long strip with size of 1.53 ± 0.11 μm
and no agglomerations, and were evenly dispersed. The re-dispersed time, sedimentation rate and pH value of the suspension were 4 s under a magnetic shaker rotating at 20 r/min, 1 and 5.0, respectively. It could go through 7-gage needle smoothly with withdrawal volume of 9.9 mL/min. Results:
The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration, the drug concentration above 0.15 μg/mL was last for 120 h. Its elimination half-life (T1/2ke), mean
residence time (MRT), and bioavailability were increased by 1.73, 1.62, and 2.16 times compared to Excenel®. Conclusion: The results suggested that the suspension had excellent sustained-release and will make ceftiofur hydrochloride more effective and convenient to use.
研究领域:
兽医学
·
药物制剂
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Analytical Chemistry
·
2020
·
IF 1.678
Zhenzhen Ying,Jingyao Wei,Ruijuan Liu,Fang Zhao,Yifang Yu,Xin Tian
Osimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and minimize adverse reactions. In the present study, a highly sensitive UPLC-MS/MS method was established and validated for analysis of osimertinib in rat plasma according to US FDA guideline. Separation was performed on a C18 (2.1 × 50 mm, 2.6 μm) column using a gradient elution of ammonium formate (10 mM) with 0.1% formic acid buffer (A) and ACN (B) at a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization in the MRM mode. The method was validated over a concentration range of 1–400 ng/mL for osimertinib. The intra- and interday accuracy and precision values were within ±15%. No significant degradation occurred under the experimental conditions in stability assays. There was a further investigation on the effects of multiple doses of ginsenoside Rg3 on the pharmacokinetics of osimertinib in rats for the first time. The results implied that osimertinib exhibited a slow absorption and moderate-rate elimination in rats following oral administration. Coadministeration with ginsenoside Rg3 (5 mg/kg, 7 days, i.g.) may have no effect on the pharmacokinetics of osimertinib in rats. The results provide a reference for the clinical concomitant medications of Rg3 and osimertinib.
研究领域:
药物分析
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Renjie Hui,Yueying Gao,Jingyi Liu,Haili Liu,Chunlei Tang,Bainian Feng
Heart failure (HF) is one of the most serious health problems worldwide. A new positive inotropic compound, an isonicotinylhydrazide derivative (AF-HF001) was designed recently. A liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed for the determination of the target analyte in mouse plasma. Samples were prepared by one step precipitation with ethyl acetate and stored in acetonitrile. Chromatographic analysis was carried out on a Hypersil Gold C 18 column (2.1 mm × 50 mm, 3 μm) with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. The analyte was detected by selective reaction monitoring (SRM) mode with target quantitative ion pair of m/z 292.1 → 148.2, using praziquantel as the internal standard (IS) m/z 313.1 → 203.2. Good linearity ( r = 0.995) was observed over a wide concentration range. The validation of method showed acceptable recovery and precision. The method has been then applied to a very first pharmacokinetic assay of AF-HF001 in mice.
研究领域:
药物分析
·
心血管药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2021
·
IF 1.908
Xian-Mei Song,Bing-Jie Li,Yan-Yan Zhang,Wen-Jing Ge,She-Feng Zhang,Wei-Feng Cui,Geng-Sheng Li,Rui-Feng Liang
Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.
研究领域:
药理学
·
内分泌学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Lijuan Ye,Weibin Chen,Yuan Chen,Yuqin Qiu,Jun Yi,Xiaofang Li,Qiuxiao Lin,Bohong Guo
Transdermal administration is a promising non-invasive and convenient method of drug delivery in clinic and avoid serious gastrointestinal adverse reactions. In this study, a hybrid nanocarrier was developed to facilitate transdermal delivery of drugs. The low water-soluble ketoprofen (KP) was ultrasonically loaded on functionalized multi-walled carbon nanotubes (f-MWCNTs), and the preparation process was optimized using Box-Behnken design. Then, KP-loaded f-MWCNTs composite ethosomes (f-MWCNTs-KP-ES) were prepared by a single-step injection technology. Over the study period, the preparation was verified by a series of characterizations, and ex vivo release characteristics, ex vivo permeation of rat skin and in vivo pharmacokinetics were studied. The characterization results consistently showed that f-MWCNTs-KP-ES were successfully prepared. The preparation can obviously improve the solubility of KP. Ex vivo permeation experiments showed that had a sustained release effect and the skin penetration rate of f-MWCNTs-KP-ES gel is the fastest, with a cumulative permeation amount of 602.35 ± 41.06 μg/cm 2 . In addition, both ethosomes and f-MWCNTs could increase the retention of drugs and form drug reservoirs. Fluorescence microscope images of rat skin clearly illustrated the faster and deeper penetration of f-MWCNTs composite ethosomes formulation loaded with rhodamine B (RB) (f-MWCNT-RB-ES). In vivo pharmacokinetic experiments showed the area under the drug time curve (AUC 0-t ) and elimination half-life (T 1/2β ) of f-MWCNTs-KP-ES gel group were significantly increased and prolonged compared with KP commercial gel group, respectively. The overall data indicate that the f-MWCNTs composite ethosomes formulation is a promising transdermal drug delivery system .
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2023
·Vol. 37
·期 9
·e5668
·
IF 1.8
Linjie Li,Jingxuan Tan,Yujing Du,Xixuan Li,Yongning Lv,Xuejia Zhai
A sensitive and specific high-performance liquid chromatography–tandem mass spectrometry method has been developed to determine the pharmacokinetic interactions of the antiplatelet agents aspirin and clopidogrel combined with dl -3 -n- butylphthalide. For the determination of aspirin metabolite salicylic acid, clopidogrel inactive metabolite SR26334 and NBP prototype drug in rat plasma, plasma samples were prepared by precipitation of proteins using methanol containing 0.1% formic acid, followed by centrifugation. Chromatography was performed on a C 18 column, eluting with a gradient of acetonitrile (with 0.1% formic acid)–water (with 0.1% formic acid). The detection adopted electrospray ion source and positive ion multiple reaction monitoring modes. The linear detection response range of salicylic acid is 80–80,000 ng/ml, and the linear detection response range of SR26334 and dl -3 -n- butylphthalide is 10–10,000 ng/ml. Our study revealed that dl -3 -n- butylphthalide affected the pharmacokinetics of aspirin and clopidogrel when administered to rats.
研究领域:
药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2023
·Vol. 37
·期 11
·e5729
·
IF 1.8
Hongli Mu,Wenyu Zhang,Yuanming Song,Rui Liang,Hengli Zhao,Chunhong Song,Qing Wen
In this study, an ultra-performance liquid chromatography–tandem mass spectrometry method was established for the development and validation of baloxavir acid (BXA) concentrations and the active ingredients of the antiviral drug baloxavir marboxil (BXM). Further, the method was applied to study the pharmacokinetics of BXA. BXA was determined by the electrospray ionization multiple reaction monitoring positive ion mode, and the mass-to-charge ratios ( m/z ) of BXA and internal standard baloxavir-d4 were 484.2 → 247.2 and 488.1 → 247.2. An Oasis max online column (2.1 × 20 mm, 30 μm) was used with 1% formic acid in water (A) and 2% formic acid in acetonitrile (B) as mobile phases at a flow rate of 0.5 mL·min −1 for chromatographic separation. The linearity was good in the range of 3–200 ng·mL −1 (r = 0.9994), with 3.00 ng·mL −1 lower limit of quantification. The relative standard deviation of the inter-assay precision was less than or equal to 6.51%, and the accuracy was in the range of 91.28%–104.29%. This method is suitable for the determination of BXA and for performing pharmacokinetic studies in clinical research.
研究领域:
药物分析
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）