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PubMed1988

A double-blind comparison of mefenamic acid and piroxicam in acute soft tissue injuries.

Thirty patients suffering from strains, sprains or direct soft tissue injuries were entered into a double-blind trial comparing mefenamic acid and piroxicam. Mefenamic acid was given at a dosage of 500 mg 3-times daily and piroxicam as a single daily dose of 20 mg, for a maximum of 10 days. Both drugs were effective in treating the symptoms associated with acute soft tissue injuries. There were statistically significant improvements in all parameters monitored (pain, functional capacity, sleep disturbance, local swelling and tenderness) by Day 2, except for local swelling in the mefenamic acid group and sleep disturbance in the piroxicam group. By Day 5 all parameters showed improvement. Almost all (90%) of the patients had recovered from their injury in less than 1 week. Both drugs were well tolerated, only 5 patients reporting adverse events (3 on mefenamic acid and 2 on piroxicam).

Acute Disease↗
PubMed1986

The effects of mefenamic acid on postprandial intestinal carbohydrate metabolism.

The effects of mefenamic acid on the food-induced changes in intestinal carbohydrate metabolism were determined in an attempt to elucidate the mechanism(s) by which inhibition of prostaglandin synthesis enhances the postprandial increases in intestinal blood flow and oxygen consumption. The data show that when the luminal perfusate was changed from saline to a nutrient/bile solution, there was an increase in carbohydrate utilization, which was offset by absorption of glucose from the lumen. Intravenous administration of mefenamic acid significantly increased both carbohydrate absorption and metabolism when food was placed in the lumen. Changes in carbohydrate absorption and metabolism have been shown to play and important role in determining the magnitude of glucose induced changes in intestinal blood flow and oxygen consumption. Therefore, it is possible that the ability of mefenamic acid to enhance significantly the food-induced increases in blood flow and oxygen consumption may be due in part to its effects on intestinal carbohydrate absorption and utilization.

Angiotensin II↗
PubMed2005

Experimental and computational studies of epithelial transport of mefenamic acid ester prodrugs.

PURPOSE: A series of ester derivatives of mefenamic acid were synthesized with the aim of suppressing local gastrointestinal toxicity of mefenamic acid. A computational method was used to assist the design of the prodrug and to gain insights into the structure relationship of these compounds as P-glycoprotein (P-gp) substrates. The prodrugs were studied for their enzymatic stability, bidirectional permeability across Caco-2 monolayer, and their potential as transporter modulators METHODS: Bidirectional transport studies were performed using Caco-2 cells. Compounds exhibiting an efflux ratio of > or =2 were further examined for their potential interaction with P-gp and multidrug resistance-associated protein (MRP) using verapamil and indomethacin. Calcein efflux inhibition studies were conducted to investigate the efflux mechanism of these compounds. Geometry optimization of the esters was performed, and the spatial separation of two electron donor groups of each prodrug was measured. RESULTS: Morpholinoethyl ester (3) and pyrrolidinoethyl ester (4) of mefenamic acid showed evidence of efflux mechanism. Inhibition by verapamil had a pronounced effect on the transport of 3 and 4. Indomethacin, however, completely inhibited the apical efflux of 3 but enhanced the efflux ratio of 4. Both compounds increased the ratio of cellular calcein accumulation by 3- to 5-fold over control. Consistent with the experimental data, the computational results suggest the involvement of P-gp or its interaction in 3 and 4 transport. CONCLUSIONS: Apical efflux of 3 is associated with P-gp and MRP, but the efflux of 4 involves P-gp and/or MRP. The computational approach used in this study provided the basis for P-gp substrates of compounds 3 and 4 from their electron donor subunits spatial separation.

Animals↗
PubMed1983

Double blind comparison of mefenamic acid and acetaminophen (paracetamol) in migraine.

We have assessed the role of mefenamic acid, a non-steroidal anti-inflammatory drug known to inhibit both the synthesis and actions of prostaglandins, as an analgesic in migraine by comparing it with the established analgesic paracetamol (acetaminophen) in a double-blind cross-over trial. Forty ambulant migraine patients were supplied with oral medication for six consecutive attacks; metoclopramide 10 mg was administered in all attacks, and paracetamol 500 mg and mefenamic acid 500 mg for three attacks each. The patients recorded the intensity of the headache at the time the medication was taken, and again after 3 hours, on a linear analogue scale. Twenty-two patients completed the trial satisfactorily. Seven had insufficient attacks and the remainder were lost to follow-up. The mean reduction in headache intensity was 36 +/- 11% on mefenamic acid and 27 +/- 10% (both mean +/- SEM) on paracetamol. While this difference is not quite statistically significant (0.1 greater than P greater than 0.05) there still remains a 28% probability that mefenamic acid is twice as potent as an analgesic. The responses in each individual patient to the two drugs were very closely correlated (P much less than 0.001). Our failure to demonstrate a convincing difference between the two analgesics leads us to speculate that peripheral prostaglandin mediated pain pathways, in which paracetamol is inactive, may be less important than central pathways, which are inhibited by both drugs.

Acetaminophen↗
PubMed2003

Comparison of fennel and mefenamic acid for the treatment of primary dysmenorrhea.

OBJECTIVES: To compare the effect of Foeniculum vulgare variety dulce (Sweet Fennel) vs. mefenamic acid for the treatment of primary dysmenorrhea. METHODS: A cohort of seventy women, 15-24 years old from a local university and high-school, who complained of dysmenorrhea were enrolled in this study. Ten cases were excluded due to evidence of secondary dysmenorrhea. The remaining 60 patients were graded mild, moderate and severe on the basis of a verbal multidimensional scoring system. Thirty patients with mild dysmenorrhea were also excluded from the study. Each of the 30 cases with moderate to severe dysmenorrhea was evaluated for three cycles. In the first cycle no medication was given (control cycle), in the second cycle the cases were treated by mefenamic acid (250 mg q6h orally) and in the third cycle, essence of Fennel's fruit with 2% concentration (25 drops q4h orally), was prescribed at the beginning of the cycle. These cycles were compared day by day for the effect, potency, time of initiation of action and also complications associated with each treatment modality, by using a self-scoring system. Intensity of pain was reported by using a 10-point linear analog technique. Statistical analyses were performed by the independent sample t-test, paired t-test and repeated measurement analysis method. RESULTS: In the study group the mean age of menarche was 12.5+/-1.3 years, the mean duration of menstruation was 6.6+/-1.4 days with the mean cycle days of 27+/-3. The findings observed during menses were as follows: headache in 26.7%, nausea in 63.3%, vomiting in 23.3%, diarrhea in 33.3%, fatigue in 93.3% and leaving the daily tasks undone was reported in 86.9% of the cases. Both of the drugs effectively relieved menstrual pain as compared with the control cycles (P<0.001). The mean duration of initiation of action was 67.5+/-46.06 min for mefenamic acid and 75+/-48.9 min for fennel. The difference was not statistically significant (P=0.57). Mefenamic acid had a more potent effect than fennel on the second and third menstrual days (P<0.05), however, the difference on the other days was not significant. No complication was reported in mefenamic acid treated cycles, but five cases (16.6%) withdrew from the study due to fennel's odor and one case (3.11%) reported a mild increase in the amount of her menstrual flow. CONCLUSIONS: The essence of fennel can be used as a safe and effective herbal drug for primary dysmenorrhea, however, it may have a lower potency than mefenamic acid in the dosages used for this study.

Adolescent↗
PubMed1999

Molecular structures of metal complexes with mefenamic acid.

The infrared spectra of Na and Ca complexes of mefenamic acid were investigated in the region between 4000 and 400 cm(-1). These spectra were compared with X-ray powder diffraction patterns of complexes. It is shown that the proposed structure for these complexes obtained from the infrared spectra was supported by X-ray powder diffraction measurements. Bands due to v(as)(COO)- and v(s)(COO)- stretching vibrations appear at about 1580 cm(-1) and in the range 1390-1400 cm(-1) in the infrared spectra of the samples, respectively. The values of NH deformation vibrations do not change in the spectra of mefenamic acid and its metal complexes. On the other hand, molecular mechanic calculations and conformational analysis of three compounds were also established in the present work. As a result of these theoretical studies, the atomic planes and the peak assignments of the powder diffraction patterns were determined. As a result of these experimental and theoretical investigations, it may be concluded that metal atoms are connected to the carboxyl group of the mefenamic acid.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Enhancement of dissolution and absorption of mefenamic acid by egg albumin.

The dissolution behavior and absorption of mefenamic acid following oral and rectal administration from drug:egg albumin solid dispersions have been studied in comparison with those of the drug alone. The interaction of drug with egg albumin in aqueous solution and solid state were examined by solubility analysis, dialysis experiments, and X-ray diffractometry. The results showed that the dissolution rate of mefenamic acid, and also the release of drug from witepsol H-15 suppositories, were significantly increased by using egg albumin:drug solid dispersions. Although egg albumin:drug solid dispersion enhanced the mean serum levels and the area under serum concentration-time curves after oral and rectal administration compared with those of the drug alone, no significant differences were found between the mean residence time values of drug and its solid dispersion. It was also noted that the extent of bioavailability of mefenamic acid and its solid dispersion following oral administration was significantly greater than that following rectal administration.

Administration, Rectal↗
PubMed1986

Comparison of mefenamic acid and propranolol with placebo in migraine prophylaxis.

The prophylactic effects of the antiprostaglandin agent mefenamic acid on migraine attacks were compared with propranolol or placebo in a double-blind crossover study of 29 patients. In the 17 patients who completed the trial the frequency of attacks and their total duration were significantly reduced during mefenamic acid therapy or propranolol therapy as compared to placebo. There were no significant effects of mefenamic acid or propranolol on average duration or severity of migraine attacks. The study suggests that mefenamic acid and propranolol are equally effective for migraine prophylaxis.

Adult↗
PubMed1979

Electroencephalographic affects of an anti-inflammatory analgesic: mefenamic acid.

A study of the electroencephalographic patterns observed following iv administration of increasing doses of mefenamic acid in acute experiments on curarized cats and rats and the possible modification of these effects by naloxone was carried out. Mefenamic acid produced in both species a progressive and dose-related increase of the voltage of the baseline patterns. With high doses, besides slow waves and fusiform complexes, an irritative activity with spikes and complexes of polyspikes was observed. The recovery of the basal activity was obtained within 15 min, except for the highest dose, under which the effect lasted 30 min after administration. Cats displayed a higher sensitivity than did rats. Naloxone did not modify the EEG effects of mefenamic acid, neigher in rats nor in rats. This fact suggests that the locus of action of these drugs is different. Mefenamic acid appears to act centrally with relatively short-lasting depressant effects at low doses and facilitating or stimulant effects at high doses.

Animals↗
PubMed1999

The effect of mefenamic acid on controlling irregular uterine bleeding secondary to Norplant use.

The aim of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding secondary to Norplant use. A total of 67 Norplant users attending the Family Planning Clinic of Chulalongkorn Hospital all had irregular bleeding. These women were randomly allocated into two groups. A total 34 users received mefenamic acid, 500 mg twice a day for 5 days, and placebos were given to the other 33 in the same manner. The total days of bleeding and spotting and the percentage of women in whom bleeding was stopped were analyzed in weeks 1 and 4. The percentage of subjects in whom bleeding was stopped during week 1 after initial treatment was significantly higher in the mefenamic acid group than the placebo group (76%, 27%; p < 0.001). In the follow-up period (4 weeks after initial treatment), a bleeding-free interval of > 20 days was found in 68% of the subjects treated with mefenamic acid and 33% treated with the placebo; the mean number of bleeding/spotting days was lower with mefenamic acid treatment (11.6 and 17.2 days; p < 0.05). The difference was statistically significant. It is concluded that mefenamic acid was more effective than placebo in short-term control of irregular bleeding and spotting associated with Norplant use.

Adult↗
PubMed2005

Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts.

OBJECTIVE: To compare the efficacy and tolerability of the levonorgestrel intrauterine system (LNG IUS) with mefenamic acid in the management of objective idiopathic menorrhagia. DESIGN: Phase III, Single centre, open, randomised, comparative, parallel group study. SETTING: District General Hospital in the United Kingdom. POPULATION: Fifty-one women with objective menorrhagia. METHODS: Twenty-five women randomised to receive the LNG IUS and 26 to oral mefenamic acid for six cycles. MAIN OUTCOME MEASURES: Change from baseline in menstrual blood loss (MBL), total menstrual fluid loss (TMFL) and pictorial blood loss assessment chart (PBAC) score at the third and sixth cycle of treatment. RESULTS: After six cycles the median menstrual blood loss was 5 mL in the LNG IUS group and 100 mL in the mefenamic acid group (P < 0.001). Median TMFL was 27 mL in the LNG IUS group and 157 mL in the mefenamic acid group (P < 0.001). Median PBAC score was 25 in the LNG IUS group and 159 in the mefenamic acid group. Changes in menstrual blood loss correlated strongly to changes in TMFL (r= 0.88) but PBAC correlated less well to blood loss and total fluid loss (r= 0.53 and r= 0.58). CONCLUSIONS: Both the LNG IUS and mefenamic acid significantly decreased menstrual blood loss, TMFL and PBAC scores. The LNG IUS produced greater reductions in all parameters than mefenamic acid. Comparison of the different measurements suggests that TMFL assessment may be an easier and a more relevant measure of symptom severity than menstrual blood loss.

Adolescent↗
PubMed1994

Determination of indomethacin and mefenamic acid in plasma by high-performance liquid chromatography.

Indomethacin and mefenamic acid are widely used clinically as non-steroidal anti-inflammatory agents. Both drugs have also been found effective to produce closure of patent ductus arteriosus in premature neonates. A simple, rapid, sensitive and reliable HPLC method is described for the determination of indomethacin and mefenamic acid in human plasma. As these drugs are not applied together, the compounds are alternately used as analyte and internal standard. Plasma was deproteinized with acetonitrile, the supernatant fraction was evaporated to dryness and the resulting residue was reconstituted in the mobile phase and injected into the HPLC system. The chromatographic separation was performed on a C18 column (250 x 4.6 mm I.D.) using 10 mM phosphoric acid-acetonitrile (40:60, v/v) as the mobile phase and both drugs were detected at 280 nm. The calibration graphs were linear with a correlation coefficient (r) of 0.999 or better from 0.1 to 10 micrograms/ml and the detection limits were 0.06 micrograms/ml for indomethacin and 0.08 micrograms/ml for mefenamic acid, for 50-microliters plasma samples. The method was not interfered with by other plasma components and has been found particularly useful for paediatric use. The within-day precision and accuracy of the method were evaluated for three concentrations in spiked plasma samples. The coefficients of variation were less than 5% and the accuracy was nearly 100% for both drugs.

Child↗
PubMed1980

Treatment of primary dysmenorrhea with mefenamic acid.

Thirty-five patients (16--23 years old) who had severe primary dysmenorrhea were each treated with 500 mg of mefenamic acid every eight hours for a maximum of three days during menstruation for three consecutive cycles. A total of 194 treated cycles could be evaluated, 110 cycles with mefenamic acid and 84 with placebo. Mefenamic acid produced complete relief of all the symptoms of dysmenorrhea in 31 (88.6%) patients in all 98 treated cycles and, in another two patients, moderate relief in five of the six cycles. While on placebo, only five patients (13%) experienced moderate to slight relief in 11 of the 15 cycles. It is concluded that the mefenamic acid is safe and effective in most patients for the relief of primary dysmenorrhea and represents a rational short-term therapy for this syndrome.

Adolescent↗
PubMed1993

A double-blind comparison of nimesulide and mefenamic acid in the treatment of acute upper respiratory tract infections in children.

The efficacy and safety of nimesulide suspension were evaluated in comparison with mefenamic acid in a double-blind multicentre study that recruited 100 children with acute respiratory tract infections. On entry, each child was randomly allocated to receive either nimesulide 5 mg/kg/day or mefenamic acid 5 mg/kg divided into 2 or 3 daily doses as an oral suspension, for a period of 3 to 10 days. Body temperature returned to normal on the third day for most of the nimesulide-treated patients, but only on the fifth day for the mefenamic acid group. There was a significant difference (p < 0.01) between the antipyretic activity of nimesulide and that of mefenamic acid. Furthermore, treatment with nimesulide was associated with clinically significant improvement in all inflammatory signs and symptoms observed (rhinorrhoea, nasal obstruction, pharyngeal redness, swelling of lymph nodes and cough). Adverse effects considered possibly related to treatment were recorded for 3 patients treated with nimesulide and 1 with mefenamic acid.

Acute Disease↗
PubMed2005

Mefenamic acid as a novel activator of L-type voltage-dependent Ca2+ channels in smooth muscle cells from pig proximal urethra.

The effects of mefenamic acid and Bay K 8644 on voltage-dependent nifedipine-sensitive inward Ba2+ currents in pig urethral myocytes were investigated by use of conventional whole-cell configuration patch clamp. Mefenamic acid increased the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba2+ current without shifting the position of the current-voltage relationship. Mefenamic acid (300 microM) caused little shift in the activation curve although the voltage dependence of the steady-state inactivation was shifted to more positive potentials by 11 mV in the presence of mefenamic acid. Bay K 8644 (> or = 100 nM) enhanced voltage-dependent nifedipine-sensitive inward Ba2+ currents in a concentration- and voltage-dependent manner, shifting the maximum of the current-voltage relationship by 10 mV in the hyperpolarizing direction. Bay K 8644 (1 microM) significantly shifted the voltage dependence of the activation curve to more negative potentials by approximately 9 mV although Bay K 8644 caused little shift in the steady-state inactivation curve. These results indicate that mefenamic acid increased voltage-dependent nifedipine-sensitive inward Ba2+ currents through the activation of L-type Ca2+ channels with different kinetics from those of Bay K 8644 in pig urethral myocytes.

Animals↗
PubMed1997

Comparative bioavailability of two capsule formulations of mefenamic acid.

Pharmacokinetic behavior of single dose of 2 mefenamic acid capsule formulations was studied in a randomized crossover design in 22 healthy male volunteers. Following ingestion of 250 mg of either of the products, blood samples were obtained over a 14-hour period and the serum drug concentrations were determined by an HPLC assay with ultraviolet detection at 280 nm. The parametric 90% confidence intervals of the mean value of the ratio (fendol (test)/ponstan (reference)) of pharmacokinetic parameters were 0.88-1.07, 0.94-1.19, and 0.89-1.16 for AUC zero-infinity, Cmax and T1/2. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Distribution-free point estimate for the difference in expected medians of Tmax of the 2 formulations (fendol-ponstan) was -0.5 hours with a 90% confidence interval of -1.0 to -0.25 which overlaps with the stipulated bioequivalence range of +/-0.48. The kinetic parameters a comparable to what is reported for mefenamic acid and there were no statistically significant differences in any of them when comparing the 2 products by ANOVA on log-transformed data. Although the 2 products are not equivalent regarding the secondary parameter Tmax, still the data indicate that they could be considered bioequivalent regarding rate of absorption (Cmax), extent of absorption (Cmax and AUC), and elimination (t1/2).

Adult↗
PubMed1989

Comparison between mefenamic acid and danazol in the treatment of established menorrhagia.

Forty women with established menorrhagia were treated with either mefenamic acid (500 mg thrice daily for 3-5 days in two cycles) or danazol (100 mg twice daily for 60 days) in an open parallel group randomized study. Mefenamic acid reduced mean menstrual blood loss from 160 ml to 127 ml (20%, P less than 0.01). Danazol reduced mean menstrual loss from 163 ml to 65 ml (60%, P less than 0.001). The percentage reduction in menstrual blood loss was significantly greater in the danazol group than in the mefenamic acid group, but the adverse side-effects occurred significantly more often in the danazol group (75%) than in the mefenamic acid group (30%, P less than 0.005). Overall, approximately half the women in each group were prepared to continue with the treatment they received to reduce their menstrual bleeding.

Adult↗
PubMed2004

Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users.

The objective of this double-blind, placebo-controlled study was to evaluate the effect of mefenamic acid and placebo on controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users. A total of 48 DMPA users attending the Family Planning Clinic, Chulalongkorn Hospital were studied, all had abnormal bleeding. These participants were randomly divided into two groups. A total of 23 users received mefenamic acid, 500 mg, twice a day for 5 days, and placebos were given to the other 25 in the same manner. Total days of bleeding and spotting and percentage of women in whom bleeding was stopped were analyzed in the first and the fourth week. Percentage of subjects in whom bleeding was stopped during the first week after initial treatment was significantly higher in the mefenamic acid group than the placebo group (69.6%, 40.0%; p < 0.05). During the follow-up period (4 weeks after initial treatment), the mean of the bleeding-free interval during 28 days was found to be 16.1 days in the subjects treated with mefenamic acid and 12.39 days in the placebo group. However, the difference was not statistically significant. From the results of the study, we concluded that mefenamic acid was effective in very short-term control of bleeding during DMPA use, but not effective long-term.

Adult↗