scholarly journals Pharmacokinetics and Metabolism Study of Deep-Sea-Derived Butyrolactone I in Rats by UHPLC–MS/MS and UHPLC–Q-TOF-MS

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 11
Author(s):  
Liang Wu ◽  
Chun-Lan Xie ◽  
Xian-Wen Yang ◽  
Gang Chen
Keyword(s):  
Deep Sea ◽  
Metabolic Pathways ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Rat Plasma ◽  
Food Allergies ◽  
Maximum Plasma ◽  
Metabolism Study ◽  
Aspergillus Sp ◽  
Tof Ms

Butyrolactone I (BTL-I) is a butanolide isolated from the deep-sea-derived fungus, Aspergillus sp. It provides a potential new target for the prevention and treatment of food allergies. This study aimed to investigate the metabolic and pharmacokinetic profile of BTL-I in rats. The metabolic profiles were obtained by UHPLC–Q-TOF-MS. As a result, eleven metabolites were structurally identified, and the proposed metabolic pathways of BTL-I were characterized. The main metabolites were the oxidative and glucuronidative metabolites. In addition, a sensitive UHPLC–MS/MS method was established for the quantitation of BTL-I in rat plasma (LOQ = 2 ng/mL). The method was fully validated and successfully applied to the pharmacokinetic study of BTL-I in rats after oral administration or intravenous administration. The oral bioavailability was calculated as 6.29%, and the maximum plasma concentrations were 9.85 ± 1.54 ng/mL and 17.97 ± 1.36 ng/mL for intravenous and intragastric dosing groups, respectively.

scholarly journals Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 71 ◽  
Author(s):  
Yu-Feng Yao ◽  
Chao-Zhan Lin ◽  
Fang-Le Liu ◽  
Run-Jing Zhang ◽  
Qiu-Yu Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve ◽  
Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

scholarly journals Pharmacokinetic Profile of μSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats

2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Rosario Russo ◽  
Angelo Mancinelli ◽  
Michele Ciccone ◽  
Fabio Terruzzi ◽  
Claudio Pisano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sprague Dawley ◽  
Time Curve ◽  
Maximum Plasma Drug Concentration

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (μSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t1/2), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with μSMIN Plus™ compared with animals treated with micronized diosmin. In particular, μSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for μSMIN Plus™, which may represent a new tool for CVI management.

scholarly journals The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Safety Evaluation ◽  
Rat Plasma ◽  
Leguminous Plant ◽  
Control Group ◽  
Kidney Toxicity ◽  
Flight Mass Spectrometry ◽  
Liver And Kidney ◽  
Tof Ms

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.

UPLC-MS/MS Assay for Quantification of Wedelolactone and Demethylwedelolactone in Rat Plasma and the Application to a Preclinical Pharmacokinetic Study

2021 ◽  
Vol 24 ◽  
Author(s):  
Bao-e Wang ◽  
Lin-tao Zhang ◽  
Sheng-bao Yang ◽  
Zeng-liang Xu
Keyword(s):  
Pharmacokinetic Study ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Maximum Plasma ◽  
Peak Time ◽  
Reaction Monitoring ◽  
Isocratic Elution ◽  
Elimination Half ◽  
Us Fda

Aim and Objective: Wedelolactone and demethylwedelolactone are the two major coumarin constituents of Herba Ecliptae. The objective of this work was to develop and validate a sensitive, rapid, and robust UPLC-MS/MS method for the simultaneous quantification of wedelolactone and demethylwedelolactone in rat plasma. Materials and Methods: Wedelolactone and demethylwedelolactone were extracted from rat plasma by protein precipitation with acetonitrile. Electrospray ionization in negative mode and selected reaction monitoring (SRM) were used for wedelolactone and demethylwedelolactone at the transitions m/z 312.8→298.0 and m/z 299.1→270.6, respectively. Chromatographic separation was conducted on a Venusil C18 column (50 mm × 2.1 mm, 5 μm) with isocratic elution of acetonitrile-0.1% formic acid in water (55:45, v/v) at a flow rate of 0.3 mL/min. A linear range was observed over the concentration range of 0.25–100 ng/mL for wedelolactone and demethylwedelolactone. Results: They reached their maximum plasma concentrations (Cmax, 74.9±13.4 ng/mL for wedelolactone and 41.3±9.57 ng/mL for demethylwedelolactone) at the peak time (Tmax) of 0.633 h and 0.800 h, respectively. The AUC0-t value of wedelolactone (260.8±141.8 ng h/mL) was higher than that of demethylwedelolactone (127.4±52.7 ng h/mL) by approximately 2-fold, whereas the terminal elimination half-life (t1/2) of wedelolactone (2.20±0.59 h) showed the approximately same as that of demethylwedelolactone (2.08±0.69 h). Conclusion : Based on full validation according to US FDA guidelines, this UPLC-MS/MS method was successfully applied to a pharmacokinetic study in rats.

scholarly journals Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

2015 ◽  
Vol 59 (8) ◽  
pp. 4366-4374 ◽  
Author(s):  
Quique Bassat ◽  
Bernhards Ogutu ◽  
Abdoulaye Djimde ◽  
Kirstin Stricker ◽  
Kamal Hamed
Keyword(s):  
Plasmodium Falciparum ◽  
Plasma Concentrations ◽  
Plasmodium Falciparum Malaria ◽  
Pharmacokinetic Profile ◽  
World Health ◽  
Maximum Plasma ◽  
Comprehensive Overview ◽  
Content Type ◽  
Pediatric Formulation ◽  
Health Organization

ABSTRACTSpecially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicatedPlasmodium falciparummalaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.

scholarly journals Bioavailability and pharmacokinetics of cefotaxime in Muscovy ducks

2016 ◽  
Vol 4 (1) ◽  
pp. 93 ◽  
Author(s):  
Mohamed Aboubakr
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Maximum Plasma ◽  
Mean Values ◽  
Elimination Half ◽  
Maximal Plasma ◽  
The Mean ◽  
Muscovy Ducks

The pharmacokinetic profile of cefotaxime following a single intravenous (IV) and intramuscular (IM) injection was studied in Muscovy ducks. Cefotaxime was given at a dose rate of 25 mg/kg b.wt. for both routes. After IV injection, the plasma levels of cefotaxime estimated at 0.08 h was 70.87 μg/ml, which declined gradually and cefotaxime was detected up to 10 h (0.59 μg/ml). The mean values of CL, Vdss and t1/2β of cefotaxime in muscovy ducks were 0.22 l/kg/h, 0.51 l/kg and 1.81 h, respectively. After IM injection, maximum plasma concentration (Cmax) was (14.72 μg/ml), time of maximal plasma concentration (tmax) was (2.3 h) and elimination half-life (t1/2el)was (1.77 h). Bioavailability following IM injection was 79.61%, and in vitro protein binding percent was 31.48%. A recommended IM dosage for cefotaxime in muscovy ducks would be 30 mg/kg b.wt., repeated at 12 h intervals will provide a therapeutic plasma concentrations exceeding the MIC≤0.5 µg/ml for most susceptible pathogens in ducks.

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats

2020 ◽  
Vol 22 (12) ◽  
pp. 1184-1190
Author(s):  
Preston Smith ◽  
M Katherine Tolbert ◽  
Emily Gould ◽  
Alex Taylor ◽  
Heather Knych ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Geometric Mean ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Maximum Plasma ◽  
Hemodynamic Variables ◽  
Elimination Half ◽  
Adult Cats

Objectives The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. Methods Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate ( f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. Results Sedation occurred in all cats, and was increased from baseline at 30 mins ( P <0.001). Decreases in HR occurred from 15–60 mins, ranging from 140 to 165 beats per min ( P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins ( P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins ( P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). Conclusions and relevance OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.

A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran

2015 ◽  
Vol 113 (05) ◽  
pp. 943-951 ◽  
Author(s):  
Viktoria Moschetti ◽  
Stephen Norris ◽  
Joachim Stangier ◽  
Michael Schmohl ◽  
Joanne van Ryn ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Antibody Fragment ◽  
Study Drug ◽  
Pharmacokinetic Profile ◽  
Rapid Decline ◽  
Maximum Plasma ◽  
Healthy Male ◽  
Clinical Trial Registration ◽  
Randomised Study ◽  
Dose Study

SummaryIdarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as a specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18–45 years received between 20 mg and 8 g idarucizumab as a 1-hour intravenous infusion in 10 sequential dose groups, or 1, 2 or 4 g idarucizumab as a 5-minute infusion. Subjects within each dose group were randomised 3:1 to idarucizumab or placebo. A total of 110 randomised subjects received study drug (27 placebo, 83 idarucizumab). Peak and total exposure to idarucizumab increased proportionally with dose. Maximum plasma concentrations were achieved near the end of infusion, followed by a rapid decline, with an initial idarucizumab half-life of ∼45 minutes. For the 5-minute infusions, this resulted in a reduction of plasma concentrations to less than 5 % of peak within 4 hours. Idarucizumab (in the absence of dabigatran) had no effect on coagulation parameters or endogenous thrombin potential. Overall adverse event (AE) frequency was similar for idarucizumab and placebo, and no relationship with idarucizumab dose was observed. Drug-related AEs (primary endpoint) were rare (occurring in 2 placebo and 3 idarucizumab subjects) and were mostly of mild intensity; none of them resulted in study discontinuation. In conclusion, the pharmacokinetic profile of idarucizumab meets the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. Idarucizumab was safe and well tolerated in healthy males.Clinical trial registration: http://clinicaltrials.gov/ct2/show/NCT01688830?term=NCT01688830&rank=1 (NCT01688830).

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