Concentration Of Mefenamic Acid Research Articles

Characterization of carbon nanotubes-gold nanoparticles composite film modified electrode and voltammetric determination of mefenamic acid

A novel carbon nanotubes modified electrode was fabricated, which was based on multi-walled carbon nanotubes (MWCNTs) dispersed in gold nanoparticles (AuNPs) colloid. It was observed that MWCNTs were dispersed in AuNPs colloid homogenously. Dihexadecyl hydrogen phosphate (DHP) was added into the suspension to prepare a more stable film modified electrode. The film showed net structure and had good electron-transfer function. On the composite film coated electrode, the electrochemical behavior of mefenamic acid was studied and an irreversible anodic peak was obtained, which was much larger than that on a bare glassy carbon electrode (GCE), due to the co-effect of MWCNTs and AuNPs on the electrochemical oxidation of mefenamic acid. Under the optimized conditions the anodic peak current was linear to the concentration of mefenamic acid in the range of 1.0 × 10-7 to 2.0 × 10-5 mol L-1. The detection limit was estimated to be 1.0 × 10-8 mol L-1 after 120 s preconcentration. The method was applied successfully to the determination of mefenamic acid in medicine sample.

Mefenamic acid bi-directionally modulates the transient outward K + current in rat cerebellar granule cells

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K + current ( I A) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 μM to 100 μM, mefenamic acid reversibly inhibited I A in a dose-dependent manner. However, mefenamic acid at a concentration of 1 μM significantly increased the amplitude of I A to 113 ± 1.5% of the control. At more than 10 μM, mefenamic acid inhibited the amplitude of I A without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I A, but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I A channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.

広範囲な口腔内疾患に適用可能なメフェナム酸鎮痛スプレーの調製と臨床評価

In order to relieve oral mucosal pain topically, we prepared a 2% mefenamic acid (MA) spray using carboxyvinyl polymer (CP, 0.25% and 0.5%) and compared it with a MA spray prepared using sodium polyacrylate (PANa, 0.2%). In the stability and dispersion tests, the MA content of the 0.25% and 0.5% CP sprays had not changed 28 days after preparation under 5 test conditions (4°C without shading, 25°C without shading, 37°C without shading, 4°C with shading, 25°C with shading). However, the MA content of the spray prepared using 0.2% PANa had decreased 3 days after preparation, demonstrating that CP was better as a dispersion agent. When the sprays were used for healthy volunteers, the salivary concentration of MA for the 0.5% CP spray was higher than that achieved with the 0.25% CP spray (0.25% CP : 3.47±1.03 mg, 0.5% CP : 4.98±1.23 mg, P<0.05).The clinical efficacy was tested in 89 out-patients (age ranging from 18 to 91 years) with eight different diseases exhibiting oral mucosal pain, who received the 0.25% CP spray (n=48) or the 0.5% CP spray (n=41). Sixty-one patients showed an analgesic effect on application of MA spray (0.25% CP : 30 patients, 0.5% CP : 31 patients) and the mean onset of action was 1'58±1'10 (0.25% CP : 1'56±1'13, 0.5% CP : 2'01±1'09).In the case of hyperesthesia and decubitus ulcer, the analgesic effect was 100% suggesting that regardless of the concentration, MA sprays using CP are very effective in patients with oral mucosal pain other than that due to oral mucostitis.

Pharmacokinetics of mefenamic acid in preterm infants with patent ductus arteriosus.

The pharmacokinetics of mefenamic acid (MA), 2 mg/kg, were studied in 17 preterm infants with symptomatic patent ductus arteriosus. They were given this dosage orally at 24 h intervals. There were marked inter-individual differences in some of the pharmacokinetic parameters after the first dose; peak plasma concentration (Cmax) varied from 1.2 to 6.1 micrograms/mL with a mean of 3.8 micrograms/mL, time to reach Cmax (tmax) varied from 2 to 18 h with a mean of 7.7 h and plasma half-life (t1/2) varied from 3.8 to 43.6 h with a mean of 18.7 h. The group of infants (10/17) who had ductus closure after the first dose had significantly lower clearance (P < 0.01), longer t1/2 (P < 0.01) and higher 24 h plasma concentration (P < 0.001) compared to the group of infants (7/17) who had no ductus closure after the first dose. It appeared that the plasma concentration of MA had to be above 2.0 micrograms/mL and maintained at this concentration for at least 12 h for MA associated with ductus closure in preterm infants to take effect. In view of the inter-individual variation of plasma MA concentration and the effective plasma concentration, we suggest that measurement of the plasma concentration should be done 24 h after the first dose. This might be useful for safe and effective therapy for infants with ductus closure failure after the first dose.

未熟児動脈管開存症治療のためのメフェナム酸坐剤の開発と評価：基剤による放出制御と健常人における体内動態

Two types of mefenamic acid (MA) suppositories were prepared, one with Vosco®, an oleaginous base (Vosco suppository) and another with polyethylene glycol (PEG), a watersoluble base (PEG suppository). The crystallinities of MA in the Vosco and PEG suppositories, the in vitro release behaviors of MA from them, and the pharmacokinetics of MA following their rectal administarations to healthy volunteers were respectively compared. X-ray diffractometry revealed that MA in the Vosco suppository was mainly dispersed in a crystal form, whereas MA in the PEG suppository was disseminated in the amorphous state, with the in vitro release of MA from the PEG suppository being faster. MA in the Vosco or PEG suppository was chemically stable, and the in vitro release behavior of MA from each suppository did not change after storage for 2 months at 5°C. The serum MA maximum concentration (Cmax) and the time to reach Cmax after rectal administration of the PEG suppository appeared to be respectively higher and to be shorter than those of the Vosco suppository. The areas under the serum MA concentration-time curves (AUCs) from zero time to 8 h for the Vosco and PEG suppositories were 3.2 and 4.1 μg·h/ml, respectively, and their values were not significantly different. It was concluded that the PEG suppository presented a faster release characteristic of MA than did the Vosco suppository and that the serum MA concentration profiles arising after administration of these suppositories reflected their release characteristics.

Effects of the nonsteroidal anti-inflammatory drug mefenamic acid on energy metabolism in the perfused rat liver

The action of mefenamic acid, a nonsteroidal anti-inflammatory drug, on energy metabolism in the isolated perfused rat liver was investigated. Mefenamic acid in the range between 0.1 and 1.0 mM was infused to livers from well-fed rats and from 24-hr fasted rats. The former were perfused with substrate-free Krebs/Henseleit-bicarbonate buffer, allowing the measurement of glycogenolysis and glycolysis from endogenous glycogen. The livers from 24-hr fasted rats, on the other hand, were perfused with Krebs/Henseleit-bicarbonate buffer containing fructose, thus allowing the measurement of fructolysis and glucose synthesis. Oxygen consumption was measured in both cases. When present in the range between 0.1 and 0.5 mM, mefenamic acid increased glycolysis, oxygen uptake, glycogenolysis and fructolysis. Higher concentrations, depending on the perfusion conditions, were inhibitory. Glucose production from exogenous fructose, on the other hand, was inhibited at low mefenamic acid concentrations. In general terms, the effects of mefenamic acid on energy metabolism seemed to be the primary consequence of its uncoupling action on the respiratory chain. This conclusion is supported mainly by the opposite effects on glucose synthesis (inhibition) and oxygen consumption (activation). The intracellular concentration of mefenamic acid is much higher than the extracellular one, a phenomenon which may represent binding to intracellular membrane or proteins.

Observations on and pharmacokinetic discussion of percutaneous absorption of mefenamic acid

Percutaneous absorption of a non-steroidal anti-inflammatory drug, mefenamic acid, was investigated biopharmaceutically using rabbits. The presence or absence of absorption was examined in simple ointment, macrogols ointment, hydrophilic ointment and absorptive ointment, which are listed in the Japanese Pharmacopeia. Favorable absorption was observed in the case of hydrophilic ointment, and it was also revealed that the volume of the intracutaneous reserve was large. p]The effects of the concentration of mefenamic acid, site of application, area of application and of additives in the ointments on acceleration of absorption were studied. When the concentration of mefenamic acid was more than 4.2%, the absorption was favorable. When the ointment was applied to the thigh, abdomen and back in that order, the amount of absorption increased. Although the amount of absorption increased with an increase in the area of application, no definite relationships could be found between the area of application and the amount of absorption. Concerning the additives, nicotinamide and N-methyl-2-pyrrolidone showed a favorable effect to accelerate absorption. The fraction of drug absorbed to the total drug (F) after intrarectal administration of hydrophilic ointment and absorptive ointment was compared with those after oral administration and percutaneous absorption.