Ultraviolet Spectrophotometric Determination of Phenylbutazone in Biologic Specimens

Wallace, Jack E.

doi:10.1002/jps.2600571206

Cited by 22 publications

(1 citation statement)

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“…The 2 main metabolites of phenylbutazone in plasma, oxyphenbutazone and yhydroxyphenbutazone, interfere in these assays. The permanganate oxidation method for the spec- trophotometric determination of phenylbutazone is not influenced by oxyphenbutazone (Wallace, 1968), but y-hydroxyphenbutazone gives an absorbance of about 30 % of that of an equal concentration of phenylbutazone (Jii.hnchen and Levy, 1972). Since yhydroxyphenbutazone may attain concentrations in plasma that are almost one-third of the concentration of phenylbutazone after repeated dosing of phenylbutazone (see section 2.3.3) this compound may introduce an error of about 10%.…”

Section: Methodsmentioning

confidence: 99%

Clinical Pharmacokinetics of Phenylbutazone

Aarbakke

1978

Clinical Pharmacokinetics

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More than 25 years after phenylbutazone was introduced as a non-steroidal anti-inflammatory agent, basic knowledge is still accumulating on its pharmacokinetics in man. Phenylbutazone is almost completely absorbed after oral administration. A large fraction of the drug in plasma is bound to proteins, and the drug has a small volume of distribution. Phenylbutazone is eliminated by metabolism, only 1% being excreted unchanged in the urine. Approximately 10% of a single dose of phenylbutazone is excreted in bile as metabolites. About 60% of the urinary metabolites have been identified. A novel type of drug metabolite in man, the C-glucuronide, is formed by direct coupling of the pyrazolidine ring of phenylbutazone to glucuronic acid via a C-C bond. Phenylbutazone is oxidised in a phenyl ring or in the side chain to hydroxylated metabolites, which may undergo subsequent O-glucuronidation. After a single dose, C-glucuronidation seems to be the dominant reaction, while oxidation becomes increasingly important after repeated administration. Due to different pharmacokinetic properties of the metabolites, the C-glucuronides are detected in highest concentrations in the urine, while the pharmacologically active compounds oxyphenbutazone and gamma-hydroxyphenbutazone predominate in plasma. The biological (elimination) half-life of phenylbutazone in man is long, with a mean of about 70 hours, and exhibits large interindividual and intraindividual variation. The interindividual variation is largely due to genetic factors. The intraindividual variation is dose and time dependent. In an individual there may be several critical dose levels where a change in the elimination kinetics takes place. Since there is no correlation between the plasma level and the clinical or toxic effects of phenylbutazone, there is at present no need for routine monitoring of plasma concentrations of the drug.

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Section: Methodsmentioning

confidence: 99%

Clinical Pharmacokinetics of Phenylbutazone

Aarbakke

1978

Clinical Pharmacokinetics

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Determination of phenylbutazone, tolbutamide and metabolites in plasma and urine using chemical ionization mass spectrometry

Weinkam

Rowland

Meffin

1977

Biol. Mass Spectrom.

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Quantitative analytical procedures for the analysis of phenylbutazone and tolbutamide levels in plasma have been developed which involve the addition of deuterium labeled internal standards to plasma followed by extraction and direct sample insertion into a mass spectrometer operating under chemical ionization conditions. Peak height ratios used to calculate plasma levels were determined by using either selected ion monitoring or repetitive scan data. The scan approach was used in a related procedure for the simultaneous determination of tolbutamide and two metabolites from urine. The accuracy, precision and sensitivity of the direct sample insertion approach to drug level measurement has been determined. Examples are given of data obtained in the course of pharmacokinetic studies in which this analytical approach appears to offer advantages in the analysis of multicomponent mixtures encountered in drug-drug interaction studies.

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