Opçöes para a utilizaçåo dos antiinflamatórios nåo-esteróides no manejo da psoríase artropática / The management of arthropatic psoriasis with nonsteroidal antiinflammatory

Os antiinflamatórios nåo-esteróides såo fármacos nåo-esteroidais que inibem a via da ciclooxigenase no metabolismo do ácido aracdônio, suprimindo a síntese das prostaglandinas. Algumas destas drogas exacerbam as lesöes cutâneas da psoríase (indometacina, ácido acetilsalicílico). Outros antiinflamatórios nåo-esteróides apresentam uma boa açåo farmacológica sem exacerbarem o quadro dermatológico da moléstia (naproxeno, ibuprofeno e fenilbutazona). Estas drogas proporcionaråo novas opçöes na terapêutica da psoríase artropática. Os autores relatam sua experiência no manejo da psoríase artropática com os antiinflamatórios nåo-esteróides

Pharmacokinetics of single oral doses of feprazone in patients with rheumatoid arthritis or with impaired renal clearance.

1. The pharmacokinetics of feprazone have been studied in 10 patients with rheumatoid arthritis (RA), and in a further six patients with renal impairment (RI) who were not suffering from rheumatoid disease. 2. For RA patients, the mean elimination half-life (t1/2) of feprazone after a single oral dose was 21 +/- 5 h (SD), the mean apparent clearance (Cl) was 0.012 +/- 0.009 l/h per kg, and the mean apparent volume of distribution (Vd) was 0.33 +/- 0.17 l/kg. Corresponding values for RI patients were 25 +/- 13 h, 0.016 +/- 0.011 l/h per kg, and 0.46 +/- 0.24 l/kg, respectively. 3. These results show no impairment of the elimination of feprazone in RA or RI patients; Vd and Cl are greater than in healthy young volunteers or elderly subjects, the AUC values are lower, but t1/2 values are similar in all groups. 4. It is suggested that the greater Cl and Vd, and lower AUC, in RA and RI patients may be due to renal insufficiency and decreased plasma protein binding of feprazone and its metabolite, or to induction of glucuronyl transferase activity by the prior medication, thus enhancing the formation of the major metabolite, the C(4)-glucuronide, and increasing drug elimination.

The disposition of feprazone and its hydroxylated metabolite in human volunteers.

1. 14C-Feprazone administered as a single oral dose (17 mg/subject) to each of 3 human volunteers on the 6th day of repeated dosage with unlabelled feprazone (200 mg/subject, twice daily) was excreted slowly, with only 19-38% of the dose excreted in the urine in 8 days, with a further 27-49% of the dose in the faeces. 2. 14C-Feprazone had a half-life of 30-33 h, similar to that after single dosage of unlabelled feprazone (22-33 h). The half-life for total 14C was not significantly different from that for unchanged feprazone, indicating that no metabolite with a very long half-life was formed. 3. Only feprazone and 4'-hydroxyfeprazone were detected in the plasma of subjects dosed orally with feprazone, the metabolite being characterized by mass spectrometry. The time of peak plasma concentration of feprazone was 4-5 h after dosage, and of 4'-hydroxyfeprazone was approx. 25 h. The urine contained feprazone plus its C-glucuronide, and 4'-hydroxyfeprazone plus its conjugate (glucuronide), in the ratio of approx. 5:1. 4. When 4'-hydroxyfeprazone was administered as a single oral dose to a human volunteer the plasma elimination half-life of the metabolite was 18 h, but after administration of feprazone the half-life of 4'-hydroxyfeprazone was 45 +/- 29 h (10 subjects), indicating the slow hydroxylation of feprazone and the slow excretion of 4'-hydroxyfeprazone. The clearance of feprazone was 5.2 and of 4'-hydroxyfeprazone was 5.5 ml/kg/h. 5. These studies have shown that even though enterohepatic recirculation of the drug in man is indicated, the plasma half-life of feprazone is unchanged on repeated dosage, and accumulation of the drug at a daily dosage of 2 x 200 mg, does not occur.

Have the newer NSAIDS contributed to the management of rheumatoid arthritis?

Approximately 30 non-steroidal anti-inflammatory agents are available for the treatment of rheumatoid arthritis. In this study patient acceptability of five such agents (benoxaprofen, fenbufen, feprazone, flurbiprofen, ketoprofen) is compared in groups of 50 patients with rheumatoid arthritis. Less than 40 per cent of patients continued on the prescribed drug for six months. Significantly more patients stopped fenbufen than stopped feprazone, otherwise dropout rates between the groups were similar. The overall efficacy and toxicity of most currently prescribed NSAIDs appear to be similar, and the availability of a surfeit of such agents dilutes clinical experience with any one drug. Despite subsequent events this method failed to differentiate benoxaprofen from the other agents. It would seem likely that this surfeit of similar drugs hinders detection of unusual complications, and impedes satisfactory management of inflammatory rheumatic disorders.

Feprazone in osteoarthritis: comparison of twice and 3-times daily dosage regimens.

In a double-blind crossover trial, 200 mg feprazone 3-times a day was compared with 200 mg twice a day in the treatment of osteoarthritis. There was no difference in clinical efficacy or in adverse effects between the two dosage schedules. Because of its long elimination half-life (approximately 24 hours) it is suggested that feprazone should be given in twice daily dosage and is a simple and effective treatment for osteoarthritis.

The distribution and excretion of 14C- and 3H-labelled 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) in the rat.

The distribution and excretion of radioactivity following a single or multiple oral administration of 3H-and/or 14C-4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) has been determined in rats. The daily excretion of radioactivity following a single administration (3H and 14C) or multiple doses (3H) fell to less than 1% of the dose in 4 days. A similar fall was observed at the end of 10 days continuous administration. The radioactivity in plasma reached a maximum between 2 and 4 h after administration of the drug (14C). Tissue levels were found to be effectively zero 24 h after administration of the drug for up to 10 days. The very large amounts of radioactivity lost in bile were found to correlate with blood, tissue and faecal levels.

Gas-chromatographic analysis of 4-prenyl-1,2-diphenyl-3-5-pyrazolidinedione (feprazone) at therapeutic levles in human plasma.

A specific and sensitive procedure for the determination of prenazone at therapeutic levels in human plasma has been developed. The method involves extraction of the drug from acidified plasma into chloroform. After further purification by back extraction the residue is examined on a gas-liquid chromatograph fitted with a flame ionisation detector. Tetraphenylethylene is used as an internal standard for quantitation by the relative peak height technique. Plasma levels encountered after oral ingestion of therapeutic doses are reported.