The pharmacokinetic profiles of mogrosides in T2DM rats

2021 ◽  
pp. 114639
Author(s):  
Yulong Zhang ◽  
Ying Peng ◽  
Guisheng Zhou ◽  
Xiaobo Li
Keyword(s):  
Pharmacokinetic Profiles

Naldemedine: Peripherally Acting Opioid Receptor Antagonist for Treating Opioid-induced Adverse Effects

2020 ◽  
Vol 20 (31) ◽  
pp. 2830-2842
Author(s):  
Masanao Inagaki ◽  
Toshiyuki Kanemasa ◽  
Takaaki Yokota
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Severe Pain ◽  
Lead Compound ◽  
Inhibitory Effects ◽  
Pharmacokinetic Profiles ◽  
Structure Activity ◽  
The Usa ◽  
Relationship Study ◽  
The Eu

Opioids are widely used for pain management in moderate-to-severe pain. However, opioids are associated with adverse events, such as constipation and emesis/vomiting. To reduce these undesired effects, a structure–activity relationship study of morphinan derivatives was conducted, and a promising lead compound with inhibitory effects on opioid receptors was obtained. Further improvement in the potency and pharmacokinetic profiles of the lead compound led to the discovery of naldemedine, which showed anti-constipation and anti-emetic effects against these adverse events that were induced by morphine without influencing morphine’s analgesic effect. Naldemedine was launched in Japan and the USA in 2017 and in the EU in 2019, for treating opioid-induced constipation.

scholarly journals Pharmacodynamic and pharmacokinetic profiles of a neurotensin receptor type 2 (NTS2) analgesic macrocyclic analog

2021 ◽  
Vol 141 ◽  
pp. 111861
Author(s):  
Magali Chartier ◽  
Michael Desgagné ◽  
Marc Sousbie ◽  
Charles Rumsby ◽  
Lucie Chevillard ◽  
...  
Keyword(s):  
Receptor Type ◽  
Neurotensin Receptor ◽  
Pharmacokinetic Profiles

scholarly journals METHOD VALIDATION OF RIFAMPICIN ANALYSIS IN HUMAN PLASMA AND ITS APPLICATION IN BIOEQUIVALENCE STUDY

2019 ◽  
pp. 296-303
Author(s):  
ENDANG LUKITANINGSIH ◽  
FATHUL JANNAH ◽  
RATNA BUDHI PEBRIANA ◽  
RATNA DEWI PUSPITA ◽  
TAUFIQUROHMAN . ◽  
...  
Keyword(s):  
Mobile Phase ◽  
High Performance ◽  
Bioequivalence Study ◽  
Hplc Method ◽  
Coefficient Of Determination ◽  
European Medicines Agency ◽  
Pharmacokinetic Profiles ◽  
Relative Standard ◽  
Precision And Accuracy ◽  
Bioequivalence Test

Objective: This research aims to validate the method for rifampicin analysis in plasma by using High-Performance Liquid Chromatography (HPLC) that can be used to study the bioequivalence of a generic tablet of rifampicin 450 mg “X” marketed in Indonesia. Methods: Bioequivalence test was analysed using HPLC equipped with UV-Vis detector at 377 nm. The mobile phase used was acetonitrile-phosphate buffer pH 6.8 (45:55) delivered at a flow rate of 1.5 ml/min. Bioequivalence test was conducted on a limited number of subjects (n=8). The subjects were divided into two groups randomly. The pharmacokinetic profiles of the test tablet and reference tablet were statistically calculated using SPSS program to see the test tablet and reference tablet were bioequivalence or not. Results: The developed HPLC method for rifampicin analysis in plasma was sufficiently valid based on the International Conference on Harmonization (ICH) and European Medicines Agency (EMA) guideline, with precision and accuracy values were % Relative Standard Deviation (% RSD = 1.40–13.04) and % Recovery (86.24–102.13), respectively. Meanwhile, the method was linear over studied concentration (0.05 to 10.26 µg/ml) with a coefficient of determination (R2) = 0.9984. The method also had good stability and sensitivity. The result of statistical calculation showed that the generic rifampicin tablet X was bioequivalence toward the reference tablet Rimactan 450 mg. Conclusion: The test rifampicin tablet that was, the generic tablet “X” was bioequivalence toward the reference rifampicin tablet “Rimactan”.

scholarly journals 0004 TS-142: A Novel and Potent Dual Orexin Receptor Antagonist with Sleep-Promoting Effects in Rats

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A2-A2
Author(s):  
D Kambe ◽  
H Hikichi ◽  
Y Tokumaru ◽  
M Ohmichi ◽  
Y Konno ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Half Life ◽  
Sleep Onset ◽  
Sleep Time ◽  
Sleep Onset Latency ◽  
Orexin A ◽  
Pharmacokinetic Profiles ◽  
Orexin Receptors ◽  
Elimination Half ◽  
Emg Electrodes

Abstract Introduction The orexin system plays a pivotal role in regulating sleep and wakefulness, thus, orexin receptors (OX1 and OX2 receptors) have gained much attention as promising therapeutic targets for the treatment of insomnia. We synthesized a novel and potent dual orexin receptor antagonist (DORA), ORN0829 (investigation code name as TS-142), which was designed to have short-acting effects. Here we report pharmacological and pharmacokinetic profiles of ORN0829 in rats. Methods The antagonistic activities of ORN0829 were assessed using calcium mobilization assays. Ala-orexin A-induced [Ca2+]i response was measured with CHO-K1 cells stably expressing human/rat orexin receptor. Rats implanted the EEG/EMG electrodes were orally administrated ORN0829 at doses of 1, 3 or 10 mg/kg at the dark onset and sleep-wake stages were inspected visually. In addition, pharmacokinetic profiles of ORN0829 were investigated in rats. Results ORN0829 inhibited Ala-orexin A-increased [Ca2+]i response with a Kb of 0.67/0.44 nmol/L (for human/rat OX1 receptor), and with a Kb of 0.84/0.80 nmol/L (for human/rat OX2 receptor), respectively, indicating that ORN0829 is a potent DORA with no species differences. ORN0829 dose-dependently increased total sleep time and reduced sleep onset latency at doses of 1, 3 and 10 mg/kg. Importantly, the ORN0829 levels in plasma and cerebrospinal fluid rapidly reached a maximum concentration, and decreased with an elimination half-life of less than 1 h. Conclusion The present study indicates that ORN0829 is a novel and potent DORA with sleep-promoting effects, and that it exhibits ideal pharmacokinetic profiles (rapid absorption and short half-life) in rats. A phase 2a study of TS-142 using patients with insomnia has been completed, which is presented in a separate poster. Support Taisho Pharmaceutical. Co., Ltd.

scholarly journals Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats

2014 ◽  
Vol 2 (6) ◽  
pp. 855-860 ◽  
Author(s):  
SEOK-BONG KANG ◽  
HO-SANG SHON ◽  
SOO-JIN PARK ◽  
CHANG-HYUN SONG ◽  
SAE-KWANG KU
Keyword(s):  
Pharmacokinetic Profiles

scholarly journals Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro

2007 ◽  
Vol 51 (10) ◽  
pp. 3642-3649 ◽  
Author(s):  
Beate Henrichfreise ◽  
Irith Wiegand ◽  
Ingeborg Luhmer-Becker ◽  
Bernd Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Parent Strain ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Wild Type ◽  
Resistance Development ◽  
Development Of Resistance ◽  
Pharmacokinetic Profiles ◽  
Mutant Prevention Concentration

ABSTRACT In this study we investigated the interplay of antibiotic pharmacokinetic profiles and the development of mutation-mediated resistance in wild-type and hypermutable Pseudomonas aeruginosa strains. We used in vitro models simulating profiles of the commonly used therapeutic drugs meropenem and ceftazidime, two agents with high levels of antipseudomonal activity said to have different potentials for stimulating resistance development. During ceftazidime treatment of the wild-type strain (PAO1), fully resistant mutants overproducing AmpC were selected rapidly and they completely replaced wild-type cells in the population. During treatment with meropenem, mutants of PAO1 were not selected as rapidly and showed only intermediate resistance due to the loss of OprD. These mutants also replaced the parent strain in the population. During the treatment of the mutator P. aeruginosa strain with meropenem, the slowly selected mutants did not accumulate several resistance mechanisms but only lost OprD and did not completely replace the parent strain in the population. Our results indicate that the commonly used dosing regimens for meropenem and ceftazidime cannot avoid the selection of mutants of wild-type and hypermutable P. aeruginosa strains. For the treatment outcome, including the prevention of resistance development, it would be beneficial for the antibiotic concentration to remain above the mutant prevention concentration for a longer period of time than it does in present regimens.

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