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  • 1
    ISSN: 1432-1041
    Keywords: Ximoprofen ; pharmacokinetics ; normal subjects ; hepatic disease ; renal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ximoprofen, a potent new non-steroidal anti-inflammatory agent, has been investigated in normal healthy subjects and in patients with hepatic or renal disease. After intravenous infusion of 22.8 mg to healthy subjects, plasma ximoprofen concentrations declined in a polyexponential manner with a terminal phase half-life of 1.9 h. The systemic clearance of ximoprofen was 115 ml·min−1 and the volumes of distribution were 18.0 l Vz and 13.8 l Vss. Ximoprofen was 80–90% bound to plasma proteins. The systemic availabilities (f) of orally and rectally administered doses of 30 mg of ximoprofen were 98% and 56% respectively and, in the case of the rectal dose, absorption appeared to be prolonged leading to “flip-flop” kinetics. After single oral doses of 30 mg of ximoprofen to patients with hepatic disease, half-life (2.2 h), peak plasma concentrations (1.55 μg·ml−1 cf 1.04 μg·ml−1 in healthy subjects) and areas under the curve (6.12 μg·h·ml−1 cf 3.54 μg·h·ml−1 in healthy subjects) were significantly different from those in healthy subjects. After single oral doses of 30 mg of ximoprofen to patients with renal disease, pharmacokinetic parameters of half-life (4.0 h), mean residence time (6.0 h) and area under the curve (9.2 μg·h·ml−1) were significantly different from those in healthy subjects. There were no significant differences in pharmacokinetic parameters between patients having differing degrees of renal disease. These data nevertheless suggest that accumulation of ximoprofen in hepatic or renal disease would be of slight or negligible clinical relevance and that no alteration of the dose regimen (up to 15 mg twice daily) may be required when ximoprofen is administered in these disease states.
    Type of Medium: Electronic Resource
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