Phenylbutazone and oxyphenbutazone

Competition between drugs for plasma binding sites occurs and is responsible for some of the clinically most important changes in drug distribution. Phenylbutazone and oxyphenbutazone, for example, potentiate the action of warfarin by displacement (A2) and trichloroacetic acid, a major metabolite of chloral hydrate has a similar effect (S12) and is the cause of hemorrhagic complications during coumarin therapy (A2). 

In addition to the agents in this section, sulindac and indomethacin (see Nonsteroidal Anti-inflammatory Agents monograph) and phenylbutazone and oxyphenbutazone (see individual monographs) are indicated for the treatment of gout. 

Pond et al (23) reported that the rate of metabolism of tolbutamide was decreased by chronic adminstration of certain drugs, they claimed that the tolbutamide half-life was increased by chronic adminstration of sulphaphenazole (9.5 hrs to 28.6 hrs), phenylbutazone (7.9 hrs to 23.1 hrs), and oxyphenbutazone (8.1 hrs to 30.2 hrs). The rate of elimination of tolbutamide was decreased within one to two hours after a single dose of sulphaphenazole and the half-life was increased from 9.2 hrs to 25.7 hrs. In contrast, phenylbutazone and oxyphenbutazone, adminstered as a single dose 800 mg have no immediate effect on tolbutamide elimination. It is suggested that phenylbutazone and oxyphenbutazone act by inducing a form of a cytochrome P-450 with low activity for tolbutamide hydroxylation, whereare, sulphaphenazole acts by direct inhibition of the microsomol mixed function oxidase system. 

Anonymous. Phenylbutazone and oxyphenbutazone time to call a halt. Drug Ther Bull 1984 22(2) 5-6. 

Since 1983 phenylbutazone and oxyphenbutazone have been removed from the market in many countries or have been hmited to specific indications. In 1985, Ciba-Geigy decided to stop sales of systemic dosage forms of oxyphenbutazone worldwide and to reduce the indications for phenylbutazone (SEDA-9, 85) (SEDA-10, 78). Nevertheless, phenylbutazone is still to be found in many places. Phenylbutazone and its congeners are now used only for ankylosing spondyhtis and sometimes for acute gout, psoriatic arthritis, and active rheumatoid arthritis in patients who have not responded to other therapy, including other NSAIDs. For other indications, less toxic alternatives suffice (1,2). 

Inman WH. Study of fatal bone marrow depression with special reference to phenylbutazone and oxyphenbutazone. BMJ 1977 l(6075) 1500-5. 

Lees P, Maitho T E, Taylor J B O 1985 Pharmacokinetics of phenylbutazone in two age groups of ponies a preliminary study. Veterinary Record 116 229-232 Lees R Taylor J B O, Higgins A J et al 1986 Phenylbutazone and oxyphenbutazone distribution Into tissue fluids in the horse. Journal of Veterinary Pharmacology and Therapeutics 9 204-212... 

M Stoltz, DW Oliver, PL Wessels, AA Chalmers. High-resolution solid state carbon-13 nuclear magnetic resonance spectra of mofebutazone, phenylbutazone, and oxyphenbutazone in relation to X-ray crystallographic data. J Pharm Sci 80 357-362, 1991. 

A clinical comparison of oxyphenbutazone with phenylbutazone has shown that the two drugs are similarly effective and that the incidence of side effects is the same . Other controlled trials of oxyphenbutazone have also been reported . As with amidopyrine, prolonged use of phenylbutazone and oxyphenbutazone has been restricted by the fear of dangerous side effects, particularly those on the blood and haemopoietic organs . ... 

Pinkerton, T.C. Perry, J.A. Rateike, J.D. Separation of furosemide, phenylbutazone and oxyphenbutazone in plasma by direct injection onto internal surface reversed-phase columns with systematic optimization of selectivity. J.Chromatogr, 1986, 367, 412-418... 

When more detailed interpretation of the results is required, solution-phase NMR spectra can often be useful in the assignment of resonances observed in the solid-state NMR spectrum of the same compound. At the same time, the effects of magnetic nonequivalence associated with details of the crystallography can also be evaluated. This situation has been illustrated in Fig. 11, where the solid-state spectrum reported for benoxaprofen Form I is found to exhibit both similarities and differences relative to the solution-phase spectrum [152]. Contrasts between solution-phase and solid-state NMR spectra have also been drawn for mofebutazone, phenylbutazone, and oxyphenbutazone [153]. 

The tricyclic antidepressants can delay the absorption of phenylbutazone and oxyphenbutazone from the gut, but their antirheumatic effects are probably not affected. 

The absorption of a single 400-mg dose of phenylbutazone in 4 depressed women was considerably delayed (time to maximum level, 4 to 10 hours compared with 2 hours), but the total amount absorbed (measured by the urinary excretion of oxyphenbutazone) remained unchanged when they were pretreated with desipramine 75 mg daily for 7 days. In another 5 depressed women the half-life of oxyphenbutazone was found to be unaltered by 75 mg of desipramine or nortriptyline dailyAnimal studies have confirmed that the absorption of phenylbutazone and oxyphenbutazone are delayed by the tricyclic antidepressants, probably because their antimuscarinic effects reduce the motility of the gut, - but there seems to be no direct clinical evidence that the antirheumatic effects of either drug are reduced by this interaction. No particular precautions appear to be needed. 

Phenylbutazone and oxyphenbutazone from plasma and urine Plasma is deproteinized by adding acetonitrile and centrifuging... 

Neto, L.M.R Andraus, M.H. Salvador , M.C. Determination of phenylbutazone and oxyphenbutazone in plasma and urine samples of horses by high-performance liquid chromatography and gas chromatography-mass spectrometry. J. Chromatogr. B, Biomed. Appl. 1996, 678 (2), 211-218. 

Taylor, M.R. Westwood, S.A. Quantitation of phenylbutazone and oxyphenbutazone in equine plasma by high-performance hquid chromatography with sohd-phase extraction. J. Chromatogr. A, 1995, 697 (1-2), 389 396. 

Phenylbutazone and oxyphenbutazone both inhibit DNA synthesis in normal human bone marrow cells (22) and blood dyscrasias may be related to abnormally slow oxidation of these drugs (23). The bone... 

Phenylbutazone and oxyphenbutazone can cause pulmonary oedema as a result of fluid retention, but this mechanism seems unlikely in this case. 

Phenylbutazone and oxyphenbutazone cause retention of salt and water with oedema and weight gain (27 =, 30 =). 

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