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The effect of sulfinpyrazone on the disposition of pseudoracemic phenprocoumon in humans 总被引:1,自引:0,他引:1
L D Heimark S Toon M Gibaldi W F Trager R A O'Reilly D A Goulart 《Clinical pharmacology and therapeutics》1987,42(3):312-319
The effect of sulfinpyrazone on the pharmacokinetics and disposition of the enantiomers of pseudoracemic phenprocoumon was assessed by analyzing serial plasma, urine, and fecal samples for parent drug and metabolites by GC/MS. Essentially all of the administered dose could be accounted for either as parent drug, known metabolites, or their conjugates. Phenprocoumon and the 7-hydroxymetabolite represented the major materials recovered. All drug-related materials excreted into the urine were extensively conjugated. Sulfinpyrazone treatment did not affect the hypoprothrombinemia produced by phenprocoumon nor did it significantly alter the plasma elimination kinetics of the individual (R)- and (S)-enantiomers. However, an apparent increased free fraction of both enantiomers in plasma and inhibition of 7-hydroxylation of (S)-phenprocoumon were observed in the presence of sulfinpyrazone. The results of this study are contrasted with those of a previous study on the interaction between sulfinpyrazone and the structurally similar coumarin anticoagulant warfarin. 相似文献
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Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing. 相似文献
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Gibaldi M 《The Annals of pharmacotherapy》2007,41(12):2048-2054
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From measurements of wavefront aberrations in 16 emmetropic eyes, we calculated where objects in the world create best-focused images across the central 27 (diameter) of the retina. This is the retinal conjugate surface. We calculated how the surface changes as the eye accommodates from near to far and found that it mostly maintains its shape. The conjugate surface is pitched top-back, meaning that the upper visual field is relatively hyperopic compared to the lower field. We extended the measurements of best image quality into the binocular domain by considering how the retinal conjugate surfaces for the two eyes overlap in binocular viewing. We call this binocular extension the blur horopter. We show that in combining the two images with possibly different sharpness, the visual system creates a larger depth of field of apparently sharp images than occurs with monocular viewing. We examined similarities between the blur horopter and its analog in binocular vision: the binocular horopter. We compared these horopters to the statistics of the natural visual environment. The binocular horopter and scene statistics are strikingly similar. The blur horopter and natural statistics are qualitatively, but not quantitatively, similar. Finally, we used the measurements to refine what is commonly referred to as the zone of clear single binocular vision. 相似文献
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L D Heimark L Wienkers K Kunze M Gibaldi A C Eddy W F Trager R A O'Reilly D A Goulart 《Clinical pharmacology and therapeutics》1992,51(4):398-407
Amiodarone decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Warfarin excretion products were quantified and clearance and formation clearance values calculated. Amiodarone and metabolites inhibited the reduction of (R)-warfarin to (R,S)-warfarin alcohol-1 and the oxidation of both (R)- and (S)-warfarin to phenolic metabolites. Inhibition of warfarin hydroxylation by amiodarone in human liver microsomes was compared with the in vivo results. In agreement, the in vitro data indicates that amiodarone is a general inhibitor of the cytochrome P450 catalyzed oxidation of both enantiomers of warfarin, but the metabolism of (S)-warfarin is more strongly inhibited than that of (R)-warfarin. These data suggest that the enhanced anticoagulant effect observed when amiodarone and warfarin are coadministered is attributable to inhibition of P4502C9, the isozyme of P-450 primarily responsible for the conversion of (S)-warfarin to its major metabolite, (S)-7-hydroxywarfarin. 相似文献