Advanced UPLC-MS/MS Method for the Quantification of SIPI6398 in Rat Plasma and Its Pharmacokinetic Characterization DOI Creative Commons
Chen Fan,

Shunjun Ma,

Runrun Wang

et al.

Journal of Analytical Methods in Chemistry, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 7

Published: May 6, 2024

SIPI6398 is a novel anti-schizophrenia agent with new mechanism of action and demonstrates better target selectivity safety compared to its competitors. However, few in vivo studies on the pharmacokinetics bioavailability have been performed. A rapid simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was developed for accurate quantification rat plasma. protein precipitation acetonitrile-methanol (9 : 1, v/v) used treat Chromatography performed UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 μm) at flow rate 0.4 ml/min. The mobile phase consisted acetonitrile-water (with 0.1% formic acid) gradient elution used, time 4 minutes. Quantitative analysis using electrospray ionization (ESI) positive ion detection mode multiple reaction monitoring (MRM) mode. To evaluate bioavailability, administered rats two different ways: oral (4 mg/kg) intravenous (2 administration. calibration curve UPLC-MS/MS shows excellent linearity range 1-2000 ng/mL an r value above 0.99. precision, accuracy, recovery, matrix effect, stability results all meet criteria established biological analytical methods. method successfully applied it study SIPI6398. calculated be 13.2%. These potential contribute towards more comprehensive comprehension

Language: Английский

Antiviral properties of milk proteins and peptides against SARS-COV-2: A review DOI Creative Commons
Parminder Singh, Janak Dhakal, Pavan Kumar

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 117, P. 106237 - 106237

Published: May 15, 2024

Certain milk proteins and peptides exhibit promising immunogenic antiviral properties, particularly against coronaviruses like SARS-CoV-2. Amidst the global pandemic, these bioactive components present potential alternatives for combating viral diseases. Milk are known to play important roles functioning in various stages of SARS-CoV-2 replication cycle, including entry, endocytic processes, replication, cell signaling modulation. Notably, bovine lactoferrin, is reported synergistically enhance effects remdesivir, an FDA-approved anti-SARS-CoV-2 drug. Peptides derived from have demonstrated some efficacy both vitro silico studies. While findings highlight as natural agents, further validation through vivo studies clinical trials imperative determine their efficacy, safety, optimal dosages. This review provides a comprehensive exploration specific peptides.

Language: Английский

Citations

2
CYP3A4 drug metabolism considerations in pediatric pharmacotherapy DOI Creative Commons

Marin Vander Schaaf,

Kyrle Luth,

Danyelle M. Townsend

et al.

Medicinal Chemistry Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme involved in the Phase I metabolism of numerous medications used clinical practice. Its potential significance pediatric pharmacotherapy underscored by unique metabolic profile children, which differs markedly from adults, especially neonates, infants, and young children due to developmental changes activity. This review explores critical role CYP3A4 drugs population, with particular focus on combination drug therapies. Given high for drug-drug interactions therapies, understanding modulation activity essential optimizing therapeutic outcomes minimizing adverse effects. paper further examines structural similarities between these bergamottin, known inhibitor found citric fruits such as grapefruit. Variability activity, influenced genetic polymorphisms, stage, external factors, necessitates careful consideration prescribing management children. corroborates need personalized medicine approaches enhanced pharmacovigilance ensure safe effective use CYP3A4-metabolized population. Graphical

Language: Английский

Citations

2
Evaluation of Potency and Metabolic Stability of Diphyllin-derived Vacuolar-ATPase Inhibitors DOI Creative Commons

Laura M. Sanford,

Patrick T. Keiser, Naoaki Fujii

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116537 - 116537

Published: May 28, 2024

Diphyllin is a naturally occurring lignan comprised of an aryl naphthalene lactone scaffold that demonstrates beneficial biological activities in disease models cancer, obesity, and viral infection. A target diphyllin derivatives the vacuolar ATPase (V-ATPase) complex. Although diphyllin-related natural products are active with vitro for entry, potencies unknown pharmacokinetic properties limit well-designed vivo evaluations. Previous studies demonstrated have utility blocking Ebola virus cell entry pathway. However, shows limited potency poor oral bioavailability mice. An avenue to improve was used new library synthetic diphyllin. exploiting ether linkages at 4-position one-to-three carbon spacers oxygen or nitrogen atom provided compounds EC

Language: Английский

Citations

1
Pharmacokinetics of IMM‐H012 in rats using ultra‐performance liquid chromatography‐tandem mass spectrometry DOI

Shujuan Wu,

Jialei Wu,

Longquan Lin

et al.

Biomedical Chromatography, Journal Year: 2024, Volume and Issue: 38(8)

Published: May 28, 2024

Abstract The present study examined the pharmacokinetics of IMM‐H012 in rat plasma, utilizing ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile–0.1% formic acid water) with gradient elution used to achieve chromatographic separation a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS utilized positive mode. Based on findings, lower limit quantification 2 ng/mL, linearity found be acceptable within range 2–2000 ng/mL ( R > 0.995). intra‐day inter‐day precision relative deviation less than 14% plasma. matrix effect 102%–107%, accuracy ranged from 92% 113%. Pharmacokinetics rats after oral administration successfully studied UPLC‐MS/MS.

Language: Английский

Citations

1
New drugs appearing on the market in 2023: molecules containing fluorine and fragments of tailor-made amino acids DOI Creative Commons
Jianlin Han, Alicja Wzorek, Gagan Dhawan

et al.

Ukrainica Bioorganica Acta, Journal Year: 2024, Volume and Issue: 19(1), P. 3 - 20

Published: June 30, 2024

This article profiles eight new FDA-approved drugs containing fluorine along with the fragments of amino acids or their derivatives. These pharmaceuticals include Eflornithine, Lotilaner, Leniolisib, Fezolinetant, Nirmatrelvir, Repotrectinib, Nirogacestat, and Pirtobrutinib, representing such therapeutic areas as cancer, neuromuscular disorder, immunodeficiency, virology, infectious diseases. Importance fluorination, acid residues well chirality in design is highlighted

Language: Английский

Citations

1
Abnormally Elevated Blood Tacrolimus Level Following the Concomitant Use of Nirmatrelvir/Ritonavir With Extended-Release Tacrolimus in a Post-lung Transplant Patient: A Case Report and a Literature Review DOI Open Access

Hikari Yoshida,

Takumi Umemura,

Soichiro Ito

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Although nirmatrelvir/ritonavir (NMV/r) reportedly increases blood levels of tacrolimus (TAC) due to CYP3A4 inhibition and other factors, reports on the use NMV/r in combination with hydrate extended-release capsules (TAC-ER) lung transplant patients are limited. Herein, we present a case post-lung transplantation elevated trough TAC after concomitant NMV/r. A woman her 60s had undergone transplantation. She coronavirus disease 2019 (COVID-19) was co-administered TAC-ER, level controlled at approximately 4 μg/mL. Upon co-administration patient developed diarrhea vomiting hospitalized. TAC-ER discontinued day 6, measured 8 risen above 100 ng/mL. This gradually decreased 17.8 ng/mL 11 2.4 15; therefore, resumed 2.5 mg/day. On 18, 5.2 ng/mL, which within target range, discharged 19. is first report NMV/r, who showed abnormally high detection limit. In using transplantation, it may be useful confirm that below effective therapeutic range before resuming safely.

Language: Английский

Citations

0
The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience DOI Creative Commons
Huanxi Zhang, Wenrui Wu, Yitao Zheng

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: Sept. 16, 2024

Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated.

Language: Английский

Citations

0
Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study DOI
Junjun Xu, Jinmeng Li, Meng Chen

et al.

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(11), P. 1071 - 1079

Published: Sept. 26, 2024

This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting (PK) nirmatrelvir/ritonavir.

Language: Английский

Citations

0
Integrated Analysis of Remdesivir and Paxlovid in COVID-19 Patients: A Personalized Approach to High-Risk Individuals for Severe Evolution DOI Open Access
Andreea Fitero, Nicoleta Negruț, Anca Popa

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(22), P. 6670 - 6670

Published: Nov. 6, 2024

: COVID-19 led to a pandemic that has brought misery millions of people but more so those with pre-existing conditions. For this infection, several antiviral drugs were employed, including remdesivir (R) and Paxlovid (nirmatrelvir/ritonavir (NR)).

Language: Английский

Citations

0
Analysis of Nirmatrelvir Entry into Pulmonary Lining Fluid in Patients with COVID‐19: A Unique Perspective to Explore and Understand the Target Plasma Concentration of 292 ng/mL in Antiviral Activity DOI Creative Commons
Wenjing Zhang,

Lin Xia,

Zhilong Yuan

et al.

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(11)

Published: Nov. 1, 2024

ABSTRACT Background Currently, the applicant has chosen a target plasma trough concentration for nirmatrelvir, which is adjusted to 292 ng/mL based on drug's molecular weight (499.54 Daltons), its binding human proteins (69%), and in vitro antiviral EC 90 value (181 nM). However, current exposure‐effect relationships (ER) analysis of viral load patients enrolled EPIC‐HR study not revealed clinically significant trends ER. Given that lungs are primary site COVID‐19 infection, we aim further understand this exposure relationship by exploring analyzing penetration characteristics nirmatrelvir lungs. Objectives To explore activity. Methods We identified all critically ill with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment respiratory intensive care unit Changhai hospital between January 2023 October 2023. Samples bronchoalveolar lavage fluid were obtained at pre‐dose concentrations after administration (NMV). The NMV levels epithelial lining (ELF) was assessed determining NMV. Results There ELF (ELF = 0.4976*PLASMA‐ 204; R 0.96), correlation whose slope (0.4976) suggested blood‐to‐ELF ratio drug 2:1. A negative from equation indicates requires reach baseline penetrate ELF. Conclusions low permeability suggests insufficient This provides unique perspective no meaningful trend exposure‐response EPIC‐HR.

Language: Английский

Citations

0