Naproxen-probenecid interaction.
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Biomedical subjects
Publications and source records attributed to R Runkel.
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The bioavailability of cloprednol, a new systemic corticosteroid, was examined in a 12-subject crossover study in which two capsules, a tablet, and a solution were tested. Plasma was analyzed for cloprednol by a GLC-mass spectrometric method. The biological half-life, peak plasma concentration, peak time, plasma concentration at all sampling times, and plasma areas were evaluated for differences (p less than or equal to 0.05) in comparisons of pairs among the four formulations. An analysis of variance revealed that cloprednol was absorbed to the same extent from all formulations and rapidly cleared from the plasma with a half-life of 1.86 +/- 0.36 (SD) hr. All plasma profile parameters from the solid dose formulations were the same, demonstrating bioequivalence in both rate and extent of absorption. Significant differences were observed between the solution and solid dose formulations with respect to peak time, 15-min plasma concentration, and 0-30 min area, indicative of faster absorption from the solution; however, total plasma areas were the same for all four formulations. Comparison of plasma cloprednol levels in this study to those of a prior intravenous-oral dose study suggests that cloprednol was completely bioavailable from all formulations.
In earlier safety studies, naproxen, 600 mg three times daily, was administered to healthy subject without significant adverse effects. Another study demonstrated that single doses of 500 to 900 mg resulted in accelerated renal clearance and a nonlinear naproxen plasma level response after the higher doses. Our report describes the pharmacokinetics of naproxen when administered in single doses of 1, 2, 3, or 4 gm (up to eight times the clinically effective dose in rheumatoid arthritis) to healthy subjects. An increase in urinary excretion rate and continuation of the previously documented nonlinear plasma level response were observed. There were no signs that capacity to conjugate or to excrete the drug was exceeded. There were no adverse effects.
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