Abstract
A rapid, sensitive, accurate and reproducible assay procedure for the simultaneous separation and determination of phenylbutazone and oxyphenbutazone is proposed using reversed-phase, high-pressure liquid chromatography and UV detection. Acidified plasma (pH = 5) was extracted with cyclohexane-ether (1:1) and indomethacin was used as an internal standard. Plasma phenylbutazone levels after oral and intravenous drug administration were described by the two-compartment model. A pharmacokinetic model, similar to the percutaneous absorption of indomethacin, was developed to test concepts regarding the percutaneous absorption of phenylbutazone from topical ointment bases. A reasonably good agreement between experimental and calculated values was obtained by taking into account such factors as the absorption rate constant (k a), the drug release rate constant (k r) and the fraction of drug absorbed (F). The ointment bases selected for study were solution-type and suspension-type ointment bases. The good percutaneous absorption of phenylbutazone after the topical administration was obtained by using the absorption base. The optimal effect with additives in the absorption ointment base was finally attained with the addition of 1 % urea. The changes in site and size of application of the phenylbutazone ointment was also investigated and the following was found: dorsal site > abdominal site > thigh site. Increasing the size of the application area increased the percutaneous absorption of phenylbutazone.
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