Administration Of Piroxicam Research Articles

Effect of single oral administrations of non steroidal antiinflammatory drugs to healthy volunteers on arachidonic acid metabolism in peripheral polymorphonuclear and mononuclear leukocytes

The effects of a single oral administration of acetylsalicylic acid (500 mg), indomethacin (50 mg) and piroxicam (40 mg) to healthy volunteers on functional and biochemical parameters of platelets, polymorphonuclear (PMN) and mononuclear (MNL) leukocytes were evaluated. Blood was collected before and two hours after the drug intake and blood cells separated according to conventional techniques. The considered drugs almost completely suppressed the aggregation of platelets, whereas they did not affect either PMN and MNL aggregation. Superoxide anion generation by leukocytes was significantly increased after aspirin intake, whilst a significant reduction (PMN), or no effect (MNL) was observed after piroxicam and indomethacin respectively. The formation of arachidonate metabolites via the 5-lipoxygenase pathway by PMN and MNL challenged with 10 μM A23187 was unchanged following aspirin and indomethacin. In this respect a selective increase of 5-HETE and LTC 4 synthesis by MNL only was detected after piroxicam administration. The three drugs similarly reduced TXB 2 synthesis by platelets and PMN (−80% for aspirin and indomethacin, and −40% for piroxicam). As far as MNL is concerned, aspirin inhibited this metabolite by 80%, while indomethacin reduced it by 40% only. In contrast piroxicam increased TXB 2 synthesis by stimulated MNL. It can be concluded that the considered antiinflammatory drugs 1) differently affect the cyclooxygenase enzyme in platelets and leukocytes; 2) at variance with the situation in platelets, the inhibition of thromboxane formation by leukocytes is not related to modifications of cellular function; 3) the formation of arachidonate metabolites via the 5-lipoxygenase pathway is affected by piroxicam only.

Increase in OKM1+ granular lymphocytes in patients with rheumatoid arthritis.

Patients with very active rheumatoid arthritis that was being treated only with nonsteroidal antiinflammatory drugs had increased numbers of peripheral blood OKM1+ lymphocytes. In 3 patients, 90 degrees light scatter analysis revealed a double lymphocyte peak. When sorted, the high scatter peak contained a large percentage of granular lymphocytes. Patients with mild-to-moderately active rheumatoid arthritis had normal levels of OKM1+ lymphocytes, but when the drugs were discontinued, the activity of the disease and the numbers of OKM1+ cells increased. Administration of piroxicam was associated with clinical improvement and a decrease in levels of OKM1+ cells. OKM1+ granular lymphocytes are increased in some rheumatoid arthritis patients, and their numbers may correlate with clinical disease activity and/or therapy.

Piroxicam and 5'-hydroxypiroxicam kinetics following multiple dose administration of piroxicam.

Piroxicam (20 mg once daily) was administered orally to six healthy young volunteers for 15 days. Trough steady-state levels of piroxicam and 5'-hydroxypiroxicam were 5.5 and 1.2 micrograms/ml, respectively. Piroxicam's plasma half-life (54.9 h) was significantly shorter than that of 5'-hydroxypiroxicam (70.5 h). Percent unbound piroxicam and 5'-hydroxypiroxicam in plasma at steady-state averaged 1.10 and 8.07 respectively. An average of 25.2% of the dose was recovered in urine as 5'-hydroxypiroxicam; approximately two-thirds (17.2%) in the form of the glucuronide conjugate. Average steady-state plasma levels (Css) of piroxicam (7.0 micrograms/ml) were significantly higher than predicted from a previously reported single dose study (5.3 micrograms/ml).

The effect of piroxicam on locomotor activity in rats with adjuvant‐induced arthritis

AbstractTo evaluate the effectiveness of piroxicam, a clinically effective, long‐acting, nonsteroidal antiinflammatory drug, in a potential animal model of chronic nociception, the locomotor activity of arthritic rats was monitored over long periods of time by computer. Rats injected with complete Freund's adjuvant (CFA) displayed locomotor deficits as measured by both horizontal and vertical activity. In experiment 1, to test the effectiveness of piroxicam therapy in severely arthritic animals, administration of piroxicam (1‐‐10 mg/kg/day) was initiated 14 days after CFA injection and activity was recorded for 5 days. It was found that a single treatment significantly increased the mobility of the arthritic animals and the 4 additional days of treatment induced continued improvement in mobility and reduction in paw swelling. In experiment 2, to assess the effect of piroxicam on the development of the immobility associated with CFA‐induced arthritis, piroxicam administration (0.3‐‐3.3 mg/kg/day) was initiated prior to CFA injection and locomotor activity was monitored for 16 days. It was demonstrated that the activity of CFA‐injected rats severely and progressively decreased and that piroxicam significantly increased the activity of the arthritic rats, while having no effect on the activity of the nonarthritic control animals. These studies demonstrate the efficacy of piroxicam in arthritic rats and, although further investigation is necessary, demonstrate that the measurement of locomotor activity in arthritic rodents may be an important tool for the identification and evaluation of antiinflammatory/analgetic agents.

Fecal blood loss during isoxicam and piroxicam administration for 28 days

After an 11-day baseline period, groups of eight healthy men received isoxicam, 200 mg once a day, or piroxicam, 20 mg once a day, for 28 days. Fecal blood loss (FBL) was quantitated by the 51Cr-labeled erythrocyte method. FBLs for both isoxicam and piroxicam were only slightly higher than baseline for the first 3 drug dosing days, confirming the results of a previously published 4-day study of piroxicam, but FBL subsequently steadily increased, with maxima occurring for most subjects receiving isoxicam in 2 or 3 weeks and for most subjects receiving piroxicam in 3 or 4 weeks. This implies that dosing for 7 days or less, as is frequent in FBL studies of nonsteroidal anti-inflammatory drugs, may be insufficient to detect the peak drug-induced FBL. In week 4, FBL for both drugs was elevated approximately 0.6 ml/day over baseline. FBLs in week 4 were comparable to those reported for naproxen and less than those reported for indomethacin and acetylsalicylic acid. Statistical analyses of weekly plasma drug minimum concentrations suggest steady state was reached at week 2 for isoxicam and week 3 for piroxicam. There were large between-subject variations in steady-state plasma drug concentrations for both drugs. One subject in each drug group indulged in excessive alcohol consumption during the medication period, with a concomitant significant increase in FBL, which suggests exacerbation of the drug effect.

Improvement of the gastric tolerance of non-steroidal anti-inflammatory drugs by polyene phosphatidylcholine (Phospholipon® 100)

The effect of co-administration with polyene phosphatidylcholine (Phospholipon® 100) on the oral gastrotoxicity of various non-steroidal anti-inflammatory drugs (NSAIDs) was studied in the rat. The highly unsaturated phospholipid reduced gastric mucosal lesions measured 3.5 h after oral administration of aspirin, indomethacin, phenylbutazone, diclofenac, piroxicam and sudoxicam to rats which had received a 3 day bread diet followed by 24 h fasting. The extent of reduction of gastrotoxicity varied amongst the individual NSAIDs. Phospholipon® 100 also reduced gastric lesions induced by 3 day oral piroxicam and diclofenac administration. A trend towards reduction of oral diclofenac gastrotoxicity was observed following intravenous Phospholipon® 100 administration. Phospholipon® 100 H (100% saturated phosphatidylcholine) was less effective than Phospholipon® 100 in improving acute gastric tolerance to oral phenylbutazone, diclofenac and piroxicam. Administration of the NSAID-Phospholipon® 100 combination produced little change in the anti-inflammatory activities of diclofenac on carrageenan paw oedema and diclofenac and piroxicam on adjuvant arthritis in the rat. Combination with Phospholipon® 100 offers a novel means for reducing the gastric side-effects of NSAID therapy.

Administration of nonsteroidal anti-inflammatory agents in patients with rheumatoid arthritis. Effects on indexes of cellular immune status and serum rheumatoid factor levels

We have previously reported that nonsteroidal anti-inflammatory agents (NSAIAs) stimulate cellular immune responses and inhibit production of IgM rheumatoid factor in cultures of lymphocytes from patients with rheumatoid arthritis. We had 20 patients with rheumatoid arthritis stop taking NSAIAs for two weeks and then take piroxicam, a new NSAIA, for an additional ten weeks to assess the in vivo effects of NSAIAs on cellular immunity and rheumatoid factor levels. In each case, serum rheumatoid factor levels rose and phytohemagglutinin response fell when placebo was substituted for NSAIAs. Piroxicam administration was associated with a fall in rheumatoid factor levels to approximately 62% of the baseline level and with an increase in phytohemagglutinin response. The action of NSAIAs in rheumatoid arthritis may be mediated to a degree by partial correction of the disordered immunoregulation in this disease.

Administration of Nonsteroidal Anti-inflammatory Agents in Patients With Rheumatoid Arthritis

We have previously reported that nonsteroidal anti-inflammatory agents (NSAIAs) stimulate cellular immune responses and inhibit production of IgM rheumatoid factor in cultures of lymphocytes from patients with rheumatoid arthritis. We had 20 patients with rheumatoid arthritis stop taking NSAIAs for two weeks and then take piroxicam, a new NSAIA, for an additional ten weeks to assess the in vivo effects of NSAIAs on cellular immunity and rheumatoid factor levels. In each case, serum rheumatoid factor levels rose and phytohemagglutinin response fell when placebo was substituted for NSAIAs. Piroxicam administration was associated with a fall in rheumatoid factor levels to approximately 62% of the baseline level and with an increase in phytohemagglutinin response. The action of NSAIAs in rheumatoid arthritis may be mediated to a degree by partial correction of the disordered immunoregulation in this disease. (<i>JAMA</i>1983;250:2485-2488)

Piroxicam pharmacokinetics in man: aspirin and antacid interaction studies.

Pharmacokinetic studies with piroxicam, a nonsteroidal antiinflammatory agent, have been carried out following the administration of single and multiple oral doses. A plasma half-life of approximately 45 hours is observed, permitting the use of single daily doses in therapy. Enterohepatic recirculation of drug is suggested by the presence of multiple peaks in plasma concentration curves. Piroxicam is highly bound to serum proteins. The absorption and disposition of piroxicam are unaffected by the concomitant administration of aspirin and antiacids. Salicylate plasma levels are similarly unaffected by piroxicam administration.