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The time course of ventilatory adaptation to medroxyprogesterone acetate (MPA) and potential mediators of this response in plasma and lumbar CSF were determined in five healthy adult males. A significant decrease in arterial PCO2 (PACO2) at rest and exercise was noted within 48 h of drug administration with the maximum effect reached within 7 days and(More)
Following administration of a single oral dose (400 mg) or RS-ibuprofen (RS-IBP) to humans, a novel metabolite was isolated from urine and identified by tandem mass spectrometry as the taurine conjugate of IBP (IBP-Tau). The corresponding glycine conjugate was sought but was not detected in these studies. Quantitative analyses indicated that taurine(More)
Seven normal patients in labor at term were given 125 mg of methylprednisolone hemisuccinate intravenously shortly before delivery. Analysis of maternal and cord plasma samples indicated that both the hemisuccinate and free alcohol forms of the corticosteroid were transported in pharmacologic levels to the fetal compartment. Since methylprednisolone may(More)
The long-term fate of 6-alpha-methyl-methylprednisolone hemisuccinate (MPHS) placed into breast prostheses prior to implantation in humans was determined. MPHS hydrolyzes to the active form 6-alpha-methylprednisolone (MP) in water, which then diffuses out of the implant. Twenty prostheses were recovered 5.3 to 34.7 months after placement, and the solution(More)
The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the(More)
Tirilazad mesylate (Freedox, Upjohn) is the first agent of a new class of compounds called lazaroids currently under clinical investigation for its potential beneficial effects following neurotrauma. Tirilazad's therapeutic effect is due to its ability to inhibit iron-dependent lipid peroxidation. This study was conducted in Sprague-Dawley rats to determine(More)
The oxidative metabolism and chiral inversion of ibuprofen in freshly isolated rat hepatocytes was studied with the aid of a stereoselective GC/MS assay procedure. Hydroxylation of the isobutyl side chain at the subterminal carbon (to give hydroxyibuprofen) proved to be the major route of metabolism of both R(-)-ibuprofen and S(+)-ibuprofen, while formation(More)