Direct gradient reversed-phase HPLC analysis and preliminary pharmacokinetics of nalidixic acid, 7-hydroxymethylnalidixic acid, 7-carboxynalidixic acid,and their corresponding glucuronide conjugates in humans |
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Authors: | T B Vree M van den Biggelaar-Martea E W J van Ewijk-Beneken Kolmer Y A Hekster |
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Institution: | 1. Institute of Anaesthesiology, Academic Hospital Nijmegen Sint Radboud, the Netherlands 2. Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, University of Nijmegen, Geert Grooteplein Zuid 8, 6525, GA Nijmegen, the Netherlands
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Abstract: | A gradient reversed-phase high pressure liquid chromatographic analysis was developed for the direct measurement of nalidixic acid with its acyl glucuronide, 7-hydroxymethylnalidixic acid with its acyl and ether glucuronides, and 7-carboxynalidixic acid in human plasma and urine. The glucuronides and 7-carboxynalidixic acid were not present in plasma after an oral dose of 1,000 mg nalidixic acid. The acyl glucuronides of 7-carboxynalidixic acid were not present in plasma and urine. The acyl glucuronides are stable in urine at pH 5.0–5.5. The subject's urine must therefore be acidified by the oral intake of 4×1 g of ammonium chloride per day. With acidic urine, hardly any nalidixic acid was excreted unchanged (0.2%). It was excreted as acyl glucuronide (53.4% of dose), 7-hydroxymethylnalidixic acid (10.0%), the latter's acyl glucuronide (30.9%), and 7-carboxynalidixic acid (4.2%). |
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