Morniflumate in the treatment of upper airways affections in adults: a review and meta-analysis

Paleari, Davide; Cavalieri, Luca

doi:10.23736/s0026-4806.22.08200-3

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…Morni umate is clinically used for treating various conditions ranging from systemic in ammatory diseases as well as local in ammation in the upper respiratory tract and the urogenital, osteoarticular, and gastrointestinal systems (Mero et al, 2013, Paleari andCavalieri, 2022). Studies have demonstrated that both morni umate and ni umic acid exert their pharmacological effects by directly inhibiting enzymes involved in the synthesis of in ammatory prostaglandins, such as cyclooxygenase and 5-lipoxygenase (Cremonesi and Cavalieri, 2015).…”

Section: Introductionmentioning

confidence: 99%

Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite

Jeong

Jang

Lee

2023

Naunyn-Schmiedeberg's Arch Pharmacol

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This study aimed to quantify and explain inter-subject variability in morni umate pharmacokinetics and identify effective covariates through population pharmacokinetic modeling. Models were constructed using bioequivalence pharmacokinetic results from healthy Korean males and individual physiological and biochemical parameters. Additionally, we incorporated previously reported pharmacokinetic results of ni umic acid, a major active metabolite of morni umate, to extend the established population pharmacokinetic model and predict ni umic acid pharmacokinetics. Moreover, we used quantitative reports of leukotriene B 4 (LTB 4 ) synthesis inhibition in response to ni umic acid exposure to predict drug e cacy using Sigmoid E max model.Population pharmacokinetic pro les of morni umate were described using a multi-absorption (5-sequential) twocompartment model, and analysis of inter-individual variability suggested that volume of distribution in peripheral compartment was correlated with body mass index (BMI). Model simulation results showed that individuals with lower BMI had higher plasma concentrations of morni umate and ni umic acid, resulting in increased and sustained inhibition of LTB 4 synthesis. Under steady-state conditions, average plasma concentrations of morni umate and ni umic acid were 2.66-2.68 times higher in group with a BMI of 17.36 kg/m 2 compared to group with a BMI of 28.41 kg/m 2 . Additionally, inhibition of LTB 4 synthesis was 1.02 times higher in group with a BMI of 17.36 kg/m 2 compared to group with a BMI of 28.41 kg/m 2 , and the uctuation was signi cantly reduced from 6.06-0.01%. These ndings suggest that the concentration of active metabolite in plasma following morni umate exposure was lower in the obese group compared to normal group, thus potentially reducing the drug's e cacy.

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Section: Introductionmentioning

confidence: 99%

Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite

Jeong

Jang

Lee

2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Modeling population pharmacokinetics of morniflumate in healthy Korean men: Extending pharmacometrics analysis to niflumic acid, its major active metabolite

Jeong

Jang

Lee

2023

Preprint

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This study aimed to quantify and explain inter-subject variability in morniflumate pharmacokinetics and identify effective covariates through population pharmacokinetic modeling. Models were constructed using bioequivalence pharmacokinetic results from healthy Korean males and individual physiological and biochemical parameters. Additionally, we incorporated previously reported pharmacokinetic results of niflumic acid, a major active metabolite of morniflumate, to extend the established population pharmacokinetic model and predict niflumic acid pharmacokinetics. Moreover, we used quantitative reports of leukotriene B4 (LTB4) synthesis inhibition in response to niflumic acid exposure to predict drug efficacy using Sigmoid Emax model. Population pharmacokinetic profiles of morniflumate were described using a multi-absorption (5-sequential) two-compartment model, and analysis of inter-individual variability suggested that volume of distribution in peripheral compartment was correlated with body mass index (BMI). Model simulation results showed that individuals with lower BMI had higher plasma concentrations of morniflumate and niflumic acid, resulting in increased and sustained inhibition of LTB4 synthesis. Under steady-state conditions, average plasma concentrations of morniflumate and niflumic acid were 2.66–2.68 times higher in group with a BMI of 17.36 kg/m2 compared to group with a BMI of 28.41 kg/m2. Additionally, inhibition of LTB4 synthesis was 1.02 times higher in group with a BMI of 17.36 kg/m2 compared to group with a BMI of 28.41 kg/m2, and the fluctuation was significantly reduced from 6.06–0.01%. These findings suggest that the concentration of active metabolite in plasma following morniflumate exposure was lower in the obese group compared to normal group, thus potentially reducing the drug's efficacy.

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Chronic obstructive pulmonary disease and modern therapies

DEZZANI

2023

Gazz Med Ital - Arch Sci Med

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Morniflumate in the treatment of upper airways affections in adults: a review and meta-analysis

Cited by 3 publications

References 35 publications

Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite

Modeling population pharmacokinetics of morniflumate in healthy Korean men: extending pharmacometrics analysis to niflumic acid, its major active metabolite

Modeling population pharmacokinetics of morniflumate in healthy Korean men: Extending pharmacometrics analysis to niflumic acid, its major active metabolite

Chronic obstructive pulmonary disease and modern therapies

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