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At least 19 recordsLinked to original sources
PubMed1991

Use of meclofenamic acid in gynecology and obstetrics: effects on postsurgical stress.

Meclofenamic acid has been successfully used in several obstetrical and gynecological disorders sustained by a prostaglandin overproduction. A brief review of meclofenamic acid use for primary dysmenorrhea, menorrhagia, and episiotomy pain is followed by an original study of this compound in postsurgical pain and stress. Thirty gynecological patients undergoing abdominal hysterectomy and 10 pregnant women submitted to cesarean section at term were considered. In gynecological patients, meclofenamic acid suppositories (200 mg) or placebo were given every 12 h during the immediate postsurgical period; pregnant women were given the active drug only. Subjective pain was evaluated [through visual analogue scale (VAS)] in basal conditions (2 h from the end of surgery) and 2, 4, 6, 24, and 28 h from the first drug dose. At the same time, blood was drawn for the evaluation of plasma cortical levels (through coated-tube radioimmunoassay). A significant pain relief was obtained after only 4 h posttreatment both in gynecological patients and pregnant women. Meclofenamic acid was superior to placebo from 6 h after treatment and it almost suppressed subjective pain at the end of the observation period (28th h). Cortisol levels were already high at the basal evaluation and showed a further increase during the first postsurgery hours. Patients treated with meclofenamic acid had cortisol values lower than those who were treated with placebo. The former recovered normal levels after 24 h, whereas the latter already had increased values. These data demonstrate that meclofenamic acid is a safe, powerful and specific analgesic for the postsurgical period. The reduction of pain stimulation is also accompanied by a reduced activation of the neuroendocrine axis with a prompt recovery from postsurgical stress.

Adult↗
PubMed1991

Effects of meclofenamic acid in the treatment of lesions deriving from minor traumatology.

The clinical efficacy and tolerability of topical 5% meclofenamic acid gel versus placebo and oral sodium meclofenamate versus sodium naproxen were evaluated in patients affected with minor traumatologies. Ninety patients were studied: 60 were treated with either meclofenamic acid gel or placebo for 10 days, and 30 were administered with either sodium meclofenamate capsules or sodium naproxen capsules for 7 days. The 5% meclofenamic acid gel and its sodium salt in capsules proved significantly more rapid and efficient than did the reference compounds in reducing pain symptomatology. In the patients treated with 5% meclofenamic acid gel, a greater effect was seen as regards rapidity of spontaneous movement and nocturnal pain reduction. In other variables examined, that is, surface and deep hyperalgesia, and swelling and functional restriction, there was also a significantly higher efficacy than with placebo. Confirmation of the therapeutic efficacy of meclofenamic acid (sodium salt) was obtained with the capsule formulation, that was seen to exert a significant analgesic and antiphlogistic action; the onset of this action was particularly rapid. Both formulations of meclofenamic acid (gel and capsules) were found to be well tolerated. Thus, in the examined formulations, meclofenamic acid proved to be a useful tool in the treatment of lesions in the minor traumatology category.

Administration, Oral↗
PubMed1978

Prostaglandin biosynthesis in rabbit kidney medulla: inhibition in-vitro vs. in-vivo by aspirin, indomethacin and meclofenamic acid.

The non-steroidal anti-inflammatory drugs aspirin, indomethacin and meclofenamic acid were compared for their potency and duration of inhibition of prostaglandin biosynthesis in rabbit kidney medulla. Indomethacin and meclofenamic acid showed equal potency of inhibition in-vitro (IC50 0.88 micron and 0.85 micron respectively) while aspiring was a much weaker inhibitor (IC50 120 micron). In-vivo, indomethacin was the most powerful inhibitor (ID50 0.034 mg/kg) followed by meclofenamic acid (0.45 mg/kg) and aspirin (2.35 mg/kg). Studies on the duration of in-vivo inhibition by these compounds showed the effect of indomethacin and meclofenamic acid to be completely reversed within 4-6 hours. In contrast, return of kidney prostaglandin biosynthetic activity following aspirin inhibition is very slow and significant inhibition is still present 48 hours after a single aspiring injection. The inhibitory effect of aspirin in-vivo could be blocked by pretreatment with indomethacin, indicating that both drugs interact with related sites on the cyclo-oxygenase enzyme. The irreversible inhibition of the cyclo-oxygenase by aspirin as demonstrated in studies of other investigators suggests that the return of kidney prostaglandin synthetase activity after aspirin inhibition represents synthesis of new cyclo-oxygenase protein.

Animals↗
PubMed1978

Use of meclofenamic acid to investigate the role of prostaglandin biosynthesis during induced parturition in sheep.

The maternal administration of meclofenamic acid (a prostaglandin synthetase inhibitor) to pregnant sheep prevented the dexamethasone-induced delivery of live lambs and delayed delivery after foetal death in utero. Administration of meclofenamic acid had no effect on the changes in the levels of progesterone and oestrogen in the plasma which occur before lambing in response to foetal glucocorticoid. Despite normal maternal endocrine changes, increased uterine activity did not occur at the expected time, although it could be elicited by vaginal distension or by administration of oxytocin. The rates of cervical ripening and dilatation were reduced by meclofenamic acid and lambing was frequently associated with some degree of cervical dystocia. Withdrawal of meclofenamic acid did not immediately result in an increase in the level of prostaglandin F in the plasma despite the appearance of co-ordinated uterine contractions; the concentration of prostaglandin in the plasma was not raised until vaginal passage of the lambs. It is concluded that the synthesis or release of prostaglandins mediates the effects of changes in the levels of steroids in the maternal plasma on uterine contractility in sheep.

Animals↗
PubMed1991

Studies of meclofenamic acid and two metabolites in horses--pharmacokinetics and effects on exercise tolerance.

The pharmacokinetics and the effects on treadmill exercise of the anti-inflammatory drug meclofenamic acid were studied in seven Standardbred horses after single intravenous and/or oral doses. The decline in plasma concentration after a single intravenous dose of meclofenamic acid (2.2 mg/kg b.wt) was described by a two-compartment open model. The average elimination half-life was 1.4 h, the apparent volume of distribution 0.14 l/kg and the plasma clearance 0.12 l/h kg. Absorption was the rate-limiting step after oral administration. Non-compartmental analysis showed a mean absorption time of 4.3 h. The pharmacokinetics of two metabolites of meclofenamic acid were also studied in two of the horses. The elimination half-lives of the two metabolites were virtually the same in each horse (3.0 h and 3.4 h). The blood lactate response to exercise was significantly decreased after treatment with meclofenamic acid, indicating a lower utilization of the glycolytic ('anaerobic') energy contribution during exercise. Circulatory capacity was apparently unaffected with an unchanged heart rate response to exercise.

Absorption↗
PubMed1990

Effects of topical applications of meclofenamic acid and ibuprofen on bone loss, subgingival microbiota and gingival PMN response in the primate Macaca fascicularis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to alter periodontitis in both animals and humans. This study was initiated in the nonhuman primate (Nhp) model to determine the effect of two NSAIDs on preexisting gingivitis, the conversion of gingivitis to periodontitis, the associated subgingival microbiota, and the gingival PMN response. Eighteen cynomolgus monkeys were divided into three groups and treated on a blind basis with ibuprofen 8%, meclofenamic acid 5%, or placebo applied topically 5 days/week for 20 wk. After 4 wk of treatment, periodontitis was initiated in one quadrant by the placement of silk ligatures. Clinical parameters, bone loss by densitometric analysis of radiographs (CADIA), and cultural microbiology of subgingival plaque were monitored. In situ PMN chemotaxis was assessed by quantitating the PMNs which entered the sulcus in response to a challenge with n-formyl-methionyl-leucyl-phenylalanine (FMLP). No significant differences in the clinical parameters were noted by treatment groups. Radiographic bone loss was detected in all experimental sites in placebo animals as compared with 67% and 44% for ibuprofen and meclofenamic acid animals, respectively. Mean CADIA scores/animal showed a significant loss in bone density for placebo at 6 and 16 wk, no change for ibuprofen animals, and a significant increase in density for meclofenamic acid animals. The microbiota of all groups changed with ligation consistent with previous reports of disease initiation in the Nhp.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1976

Inhibition of prostaglandin F2alpha-induced reflex bradycardia and hypotension by meclofenamic acid.

Intravenous injection of prostaglandin F2alpha (4-15 mug/kg, i.v.) produces an increase in pulmonary arterial pressure in conjunction with reflex bradycardia and hypotension in the anesthetized cat. Meclofenamic acid (30 mg/kg, i.v.) inhibited the bradycardia and the reflex contribution to the systemic hypotension. Neither the PGF2alpha-induced pulmonary vasoconstriction nor the direct systemic vasodilator actions of PGF2alpha were blocked by meclofenamate. In addition, the reflex responses caused by i.v. veratrine and 5-HT were not inhibited by meclofenamate. These results suggest that meclofenamic acid selectively blocks the afferent mechanism by which PGF2alpha induces reflex bradycardia and hypotension in the cat.

Animals↗
PubMed1991

Recent acquisitions in pain therapy: meclofenamic acid.

A better utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) is possible today based on recent pharmacodynamic and pharmacokinetic studies. The analgesic action of these drugs may take place in the central nervous system (CNS). The analgesic action with a lower dose occurs earlier than the anti-inflammatory action. Some NSAIDs cause an increased level of plasmatic bendorphines in humans. NSAIDs not only have antiprostaglandin action, but also may block the release of substance P. The NSAIDs may be useful for headache, dysmenorrhea, rheumatic disease and in cancer pain therapy. For the safe use of NSAIDs the previous anamnestic and clinical features of the patient must be considered, and a high therapeutic level must be satisfied. Considering this goal, the authors examine pharmacologic and clinical behavior of meclofenamic acid.

Animals↗
PubMed1991

Interactions between oleic acid and drug competitors influence specific binding of thyroxine in serum.

Long chain nonesterified fatty acids and various drugs may share albumin-binding sites in common. We questioned whether serum binding of T4 could be indirectly influenced by displacement of drug competitors from these sites by nonesterified fatty acids. The influence of oleic acid on drug-induced inhibition of [125I]T4 binding was measured by equilibrium dialysis, using undiluted serum in order to avoid dilution-related artefacts. Oleic acid (1 mmol/L) alone did not inhibit serum protein binding of T4, but this concentration augmented the inhibitory effects on T4 binding of diflunisal, mefenamic acid, meclofenamic acid, and aspirin. This effect increased with increasing concentrations of mefenamic acid, meclofenamic acid, and furosemide. The T4-displacing effect of fenclofenac was not augmented by oleic acid. The mechanism of these interactions was studied by examining 1) oleic acid effects on drug binding, and 2) drug effects on oleic acid binding in undiluted serum. Increments in added oleic acid (0.5-2.0 mmol/L) progressively increased the mean unbound fractions of [14C]aspirin, [14C] diflunisal, and [14C]furosemide, but did not displace [14C]fenclofenac. At the relevant total and free drug concentrations, the inhibitory effect of oleic acid on drug binding and its influence on drug-induced displacement of T4 were concordant in the order: meclofenamic acid greater than aspirin greater than mefenamic acid greater than diflunisal greater than furosemide greater than fenclofenac. In contrast, drug-induced increases in the unbound fraction of [14C]oleic acid did not correlate with augmentation of T4 displacement. We conclude that synergistic effects of oleic acid and drugs on T4 binding result from drug displacement by oleic acid, rather than the reverse effect. Hence, substances that increase the unbound concentration of a competitor by displacing it from albumin can increase its T4-displacing potency. Interactions between various ligands may exert a greater hormone-displacing effect than the sum of each alone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium.

Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) approved for use in arthritis (osteo and rheumatoid), analgesia (mild to moderate pain), dysmenorrhea, and heavy menstrual blood loss (menorrhagia). At least three different biochemical effects have been defined for meclofenamic acid. It is a potent inhibitor of the enzyme cyclooxygenase, thereby inhibiting the production of prostaglandins. It also inhibits the release of 5-HETE and LTB4 from human neutrophils stimulated with calcium ionophore and antagonizes the response of tissues to certain prostaglandins. These mechanisms may explain in part the pharmacological profile and clinical effectiveness of this compound. The rapid onset of activity of meclofenamic acid and its duration of action may be the result of its pharmacokinetic profile. Sodium meclofenamate is completely bioavailable from capsules relative to an oral suspension dosage form. Maximum meclofenamic acid plasma concentrations are achieved in 0.5-2 h following doses of capsules. Meclofenamic acid is extensively metabolized. One of the metabolites, metabolite 1, is approximately 20% as active as the parent compound in inhibiting cyclooxygenase activity in vitro. This metabolite accumulates in plasma during repeated dosing. It is possible that this metabolite may contribute to at least some of the activity observed following administration of sodium meclofenamate.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Clinical experience in the treatment of dental pain.

Good dental analgesia requires drugs that are endowed with strong and fast activity and that are well tolerated. In addition, optimal analgesia should essentially be of the peripheral type, thereby eliminating the risk of sedation that may cause unpleasant effects on the patient's daily life. Meclofenamic acid is among those substances whose analgesic effect is more evident than that of anti-inflammatory action. The mechanism of action of meclofenamic acid makes it distinctly different from other nonsteroidal anti-inflammatory drugs (NSAIDs) in that it inhibits the metabolic pathways of arachidonic acid and, at the same time, antagonizes the effects of prostaglandins at the peripheral receptor level. A number of controlled clinical trials showed that meclofenamic acid is an excellent analgesic, offering good tolerability when used in oral surgery, dysodontiasis, avulsion of the third impacted molar, and periodontitis. The following report is a presentation of results obtained in a controlled clinical trial in which the speed of pain relief was assessed in 20 patients suffering from acute periodontitis. The patients were treated orally with a single dose of meclofenamate sodium (100 mg) or with piroxicam-beta-cyclodextrin (20 mg). The intensity of the drug's analgesic effect was measured at 0.5, 1, 2, 4, and 6 h after administration. After initial testing, meclofenamate sodium was found to be significantly more effective than piroxicam-beta-cyclodextrin. Both the physician and patient found this drug to be considerably better. Pain relief after treatment with meclofenamate sodium was clinically and statistically faster than piroxicam-beta-cyclodextrin, and both drugs were found to be well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Dimethylphenylpiperazinium (DMPP)-induced relaxation and elevation of cyclic GMP content in canine lower esophageal sphincter (LES).

Cyclic GMP has been proposed as an intracellular mediator of neuronally-induced relaxation in lower esophageal sphincter (LES) smooth muscle. If cyclic GMP is indeed an intracellular messenger, then agents that activate enteric neurons of the sphincter [e.g. the ganglionic nicotinic receptor agonist dimethylphenylpiperazinium (DMPP)] also should cause a relaxation that is associated with an increase in cyclic GMP content. In isolated smooth muscle strips of canine LES, DMPP produced a rapid relaxation that was accompanied by a significant (P less than 0.05) increase in cyclic GMP content with no change in cyclic AMP content. Pretreatment of tissues with either tetrodotoxin or hexamethonium antagonized both the DMPP-induced relaxation and the associated increase in cyclic GMP. The combination of phentolamine and meclofenamic acid also antagonized both the relaxation and the elevation of cyclic GMP produced by DMPP. Electrical field stimulation (EFS)-induced relaxation and elevation in cyclic GMP was unaltered by meclofenamic acid and phentolamine. In conclusion, DMPP (like neuronal electrical activation) relaxed isolated canine LES through an enteric neuronal inhibitory pathway. The presence of phentolamine and meclofenamic acid did not affect EFS-induced effects, but blocked both the relaxation and the increase in cyclic GMP produced by DMPP, suggesting a more complicated pathway for DMPP in the release of inhibitory transmitter.

Animals↗
PubMed1977

Stimulation of adenosine 3':5'-monophosphate formation by prostaglandins in human astrocytoma cells. Inhibition by nonsteroidal anti-inflammatory agents.

Prostaglandins (PG) of the E series and catecholamines stimulate adenosine 3':5'-monophosphate (cAMP) formation in human astrocytoma cells (1321N1). These two classes of effectors activated adenylate cyclase upon interaction with different receptor systems. No evidence for a mediatory role for PG in the action of catecholamines was found. PG interacted with 1321N1 cells with an order of potency of PGE1 = PGE2 greater than PGA1 greater than PGF2 alpha. The effect of combinations of the various PG indicated that all efficacious PG interacted with a common receptor. 7-Oxa-13-prostynoic acid and indomethacin were shown to be competitive inhibitors of the effect of PGE1 with Ki values of 4 and 150 micron, respectively. These two compounds did not inhibit the effect of isoproterenol. Polyphloretin phosphate caused a complex pattern of inhibition of the effects of PGE1 and at higher concentrations also inhibited the effects of isoproterenol. The mefenamate class of nonsteroidal anti-inflammatory agents was found to inhibit the effects of PGE1 with a potency order of meclofenamic acid greater than flufenamic acid = mefenamic acid. The inhibitory action of meclofenamic acid was complex involving specific, but partial, insurmountable antagonism of PGE1 as well as competitive inhibition of PGE1 effects. At higher concentrations of meclofenamic acid a nonspecific inhibition of the effects of both PGE1 and isoproterenol was observed. These studies suggest that the inhibition by nonsteroidal anti-inflammatory agents of the physiological effects of PGE1 in animals may occur, at least in part, at the level of adenylate cyclase. The possibility that multiple classes of adenylate cyclase-linked PGE receptors might exist in nature is discussed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Clinical experiences in the treatment of pain in rheumatology.

Meclofenamic acid is an analgesic endowed with anti-inflammatory properties. Its main activity is the combined inhibition of leukotrienes and prostaglandins synthesis, yet it is also able to antagonize the peripheral effects of prostaglandins. This particular feature explains why the effect of this drug is so fast, especially when administered orally. The pharmacological properties and good tolerability of meclofenamic acid propose the use of this drug for the treatment of various types of pain, particularly at osteoarticular localization. Recent comparative studies with meclofenamic sodium versus placebo, indomethacin, oxyphenbutazone, and diclofenac confirmed that meclofenamate sodium is very effective, significantly reducing pain as well as the subjective and objective symptoms accompanying it. The findings of these studies have also highlighted a particularly favorable safety profile. Our study primarily focused on assessing the effectiveness and tolerability of this drug in 82 patients affected with extraarticular rheumatism localized in various sites. Meclofenamic acid (as a sodium salt) was orally administered in doses of 100 mg twice daily for 2 weeks. The assessment of the drug's clinical effectiveness took into account the various aspects of pain (spontaneous, on motion, due to active contrasted movements) and quantified it using a 5-point rating scale (0 = absence of pain; 5 = very intense pain). At the end of the 2-week observation period, both the investigator and the patient gave their opinion as to the effectiveness and tolerability of the drug. The treatment was found to be highly effective in reducing pain in 59.7% of the patients, regardless of the nature and location of the rheumatic process. Tolerability was rated good-to-excellent in 72% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1975

Factors influencing the effect of hormones on the accumulation of cyclic AMP in cultured human astrocytoma cells.

The characteristics of the effects of catecholamines, prostaglandins, and adenosine on the adenosine 3',5'-monophosphate (cAMP) content of human astrocytoma cells are described. Catecholamines interact with a typical beta-adrenergic receptor, i.e., the order of potency of catecholamines is isoproterenol larger than or equal to epinephrine greater than norepinephrine greater than dopamine, and propranolol is an inhibitor but phentolamine is not. The prostaglandins interact with a receptor that recognized PGE-1, PGE-2, and PGA-1 but not PGF-2-alpha. The effects of PGE-1 are blocked by 7-oxa-13-prostynoic acid, indomethacin, and meclofenamic acid in a rapid, reversible manner. The cells contain another adenylate cyclase-linked receptor that recognizes adenosine and the adenine nucleotides but not guanosine, deoxyadenosine, or adenine. Theophylline and other methylxanthines are competitive inhibitors of the effect of adenosine. Each class of effector appears to stimulate adenylate cyclase by interacting with a structure-specific receptor. This follows from the observation that the effect of each class of agonists can be blocked selectively by the various inhibitors and is consistant with the observation that co-addition of different agonists results in additive effects on accumulation of cAMP. The magnitude of the effect of any of the classes of agonists can be influenced by a variety of factors, some of which may be related to the peculiarities of growth in culture: (1) The cells secrete cAMP into the medium, and the magnitude of this secretion for a given rise in intracellular cAMP is different for different agonists. (2) The exposure of the cells to catecholamines or prostaglandins leads to a loss of responsiveness to a subsequent challenge by the same agonist. The magnitude of the agonist-induced loss of responsiveness is dependent on the concentration of the agonist and the time of exposure. The process is at least partially agonist specific in that exposure of cells to isoproterenol can lead to greater than 90% loss in catecholamine responsiveness with less than 20% loss in responsiveness to prostaglandins. (3) The responsiveness of the cells also changes as a function of the age of the culture and as a function of cell density. (4) Finally, it can be demonstrated that cells maintained in culture for prolonged periods (months to years) may lose responsiveness to specific agonists while responsiveness to other agonists remains unchanges or actually increases. The advantages and disadvantages of the use of cells in culture for studies of the regulation of cAMP metabolism are discussed.

Adenine↗
PubMed1979

Contribution of prostaglandins to muscle blood flow in anesthetized dogs at rest, during exercise, and following inflow occlusion.

The role of locally formed cyclo-oxygenase products (endoperoxide intermediates, prostaglandins, or prostacyclins) in resistance to blood flow was studied in the hindlimbs of anesthetized dogs during rest, during exercise, and following release of inflow occlusion. Meclofenamic acid, indomethacin, or sodium meclofenamate reduced mean resting blood flows of 86, 113, and 118 ml/min to 54, 82, and 67 ml/min, respectively. Inhibitors of prostaglandin synthesis reduced the vasodilator response to arachidonic acid by 81%. In addition, prostaglandin synthesis inhibitors attenuated the hyperemic responses following inflow occlusions in the resting hindlimb. The attenuation was most marked following a 1-second occlusion (74%) and progressively less following a 10-second (44%) and a 300-second (24%) occlusion. However, the portion of the total postocclusive hyperemic response attributable to prostaglandins was constant and independent of occlusion duration. Inhibition of prostaglandin synthesis did not affect the hyperemia of exercise, but reduced significantly the postocclusion hyperemia that followed the release of a 1-second (63%) and a 2-second (43%) period of inflow occlusion in the exercising hindlimb; attenuation was minor following a 10-second occlusion (10%). In three of four exercising hindlimbs, the portion of the postocclusion hyperemia attributable to prostaglandins was inversely related to the duration of the occlusion. These data indicate that locally synthesized cyclo-oxygenase products, possibly prostaglandins, are important in the maintenance of blood flow in resting but not exercising muscle, contribute significantly to postocclusive hyperemia in resting and exercising hindlimbs, and mediate the hyperemia that follows occlusions of 5 seconds or less in resting and 2 seconds or less in exercising hindlimbs.

Animals↗
PubMed1978

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals↗
PubMed1975

A sensitive method for the comparative bioassay of nonsteroidal anti-inflammatory compounds in adjuvant-induced primary inflammation in the rat.

A method for the comparative bioassay of nonsteroidal anti-inflammatory agents is presented which exploits the early inflammation induced by injection of adjuvant into the plantar surface of a hind paw of the rat. The inflammation reaches a peak on the 4th postinjection day. Daily treatment with nonsteroidal anti-inflammatory agents reduces paw volumes and the associated impairment of body growth with optimal improvement on the 4th postinjection day. In this model, phenylbutazone has shown significant activity at doses as low at 1.33 mg/kg/day. Statistically valid comparative assays conducted at dose levels equivalent to or below those used in human therapy yield potency ratios with relatively narrow confidence limits. Potencies relative to phenylbutazone for inhibiting primary adjuvant-induced inflammation are: aminopyrine, 0.066 (0.36-0.11)95%; aspirin, 0.087 (0.039-0.19)95%; mefenamic acid, 0.98 (0.64-1.6)95%; flufenamic acid, 13 (7.4-26)95%; meclofenamic acid, 23(16-33)95%; and indomethacin, 53 (35-82) 95%. Ancillary and sometimes quantitative information is also provided by the improvement in well being of the animals as reflected in body weight changes with treatment.

Aminopyrine↗