Pharmacokinetics of nalidixic acid in man: Hydroxylation and glucuronidation
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Nalidixic acid is metabolized by hydroxylation to 7-hydroxymethylnalidixic acid∥ and then by oxidation to 7-carboxynalidixic acid.∥ The half-lives of the two elimination phases of nalidixic acid are 0.75 and 2.5 h. The apparent half-lives of the metabolite 7-hydroxymethylnalidixic acid are 2.5 and 5.5 h. Plasma protein binding of nalidixic acid is 95% and that of 7-hydroxymethylnalidixic acid 65%. The renal clearance of nalidixic acid varies between 2 and 25 ml/min and that of 7-hydroxymethylnalidixic acid between 37 and 162 ml/min. Of nalidixic acid 42% is glucuronidated and 40% hydroxylated. Of the hydroxy metabolite 57% is glucuronidated and 32% excreted unchanged. 7-Carboxynalidixic acid is excreted in the urine and is not glucuronidated. The variations in the glucuronidation/ hydroxylation ratio of nalidixic acid and the glucuronidation/renal excretion ratio of the 7-hydroxymethyl metabolite belong to a normal distribution.
KeywordsChromatography, high pressure liquid Clearance Metabolism Nalidixic acid Pharmacokinetics Protein binding
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- 6.McChesney EW, Froelich EJ, Lesher GY, Grain AVR, Rosi D. Absorption, excretion and metabolism of a new antibacterial agent nalidixic acid. Toxicol Appl Pharmacol 1964;6:292–309.Google Scholar
- 10.Wijnands WJA, Vree TB, Van Herwaarden CLA. The effect of the 4-quinolone enoxacin on plasma theophylline concentrations. Pharm Weekbl [Sci] 1986;8:35–40.Google Scholar
- 11.Metzler CM, Elfring GL, McEwen AJ. A package of computer programs for pharmacokinetic monitoring. Biometrics 1974;572–80.Google Scholar
- 12.Anonymous. SAS User's guide. Basics 1982 Edition. Cary: SAS Institute Inc., 1982.Google Scholar
- 13.Shapiro SS, Wilk MB. An analysis of variance test for normality (complete samples). Biometrika 1965;52:591–611.Google Scholar
- 18.Vree TB, Wijnands WJA, Guelen PJM, Baars AM, Hekster YA. Pharmacokinetics, metabolism and renal excretion of quinolones in man. Pharm Weekbl [Sci] 1986;8:29–34.Google Scholar