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.
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 x 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-hydroxymethyl-nalidixic acid (10.0%), the latter's acyl glucuronide (30.9%), and 7-carboxynalidixic acid (4.2%).
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Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, University of Nijmegen, The Netherlands.
van den Biggelaar-Martea
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M
van Ewijk-Beneken Kolmer
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EW
Hekster
Y A
YA
D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009268:Nalidixic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D005965:Glucuronates; C025188:7-carboxynalidixic acid; C012368:7-hydroxynalidixic acid; D009268:Nalidixic Acid