Pharmacokinetics of nalidixic acid in man: Hydroxylation and glucuronidation

  title={Pharmacokinetics of nalidixic acid in man: Hydroxylation and glucuronidation},
  author={T. Vree and W. Wijnands and A. M. Baars and Y. Hekster},
  journal={Pharmaceutisch Weekblad},
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… Expand
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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 itsExpand
Enhancement of nalidixic acid solubility via cosolvency and solid dispersion
Nalidixic acid is practically insoluble in water therefore the aim of this study was to study the effect of both cosolvency and solid dispersion on its solubility. Among different cosolvents, theExpand
Formulation and clinical evaluation of some new nalidixic acid topical formulations
In a novel attempt, nalidixic acid was formulated in different topical 1 % (w/w) gel and cream bases. The viscosity, pH and drug content of preparations were investigated. The highest in vitroExpand


Nalidixic acid kinetics after single and repeated oral doses
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pH-dependent rearrangement of the biosynthetic ester glucuronide of valproic acid to beta-glucuronidase-resistant forms.
It was shown that sample handling and storage conditions of ester glucuronides prior to analysis are of prime importance, since hydrolysis with beta-glucuronidase is frequently used for identification and quantification of glucuronide. Expand
Pharmacokinetics of nalidixinic acid and oxolinic acid in healthy women.
The pharmacokinetics of oral nalidixic acid and oxolinic acid administered for 7 days were studied in the same 10 healthy women on the first, third, and seventh days of the treatment and the microbiologic assay gave somewhat higher concentrations of the active drug than did the chemical assay. Expand
When studied in dogs and monkeys following long-term administration at high dose levels, nalidixic acid is found to have little tendency to accumulate in any tissue; practically all tissues have lower concentrations than those existing concomitantly in the plasma. Expand
Pharmacokinetics of nalidixic acid associated with sodium citrate.
Urine alcalinization enhanced markedly the urinary excretion of HNA, but not of NA and CNA, and the daily administration of 3 sachets of NSC each containing 0.66 g of NA seems valuable in the treatment of urinary tract infections. Expand
Pharmacokinetics of Nalidixic Acid in Old and Young Volunteers
Diminished renal function in the geriatric group may explain the slower elimination of the drug in the old subjects, and significant variations in the pharmacokinetic parameters were obtained between the two groups of volunteers. Expand
Pharrnacokinetics of nalidixinic acid and oxolinic acid in healthy wornen
The pharmacokinetics of oral nalidixinic acid (NA, 1 gm 4 times a day) and oxolinic acid (OA, 750 mg 2 times a day) administeredfor 7 days were studied in the same 10 healthy women on the first,Expand
Nalidixic acid kinetics in renal insufficiency.
The study of the urinary concentrations of NA and metabolites shows that a standard NA dosage can be used, at least in patients with mild renal insufficiency, and suggests that HNA can still be biotransformed into CNA by the impaired kidney. Expand
Determination of nalidixic acid and its two major metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography.
The applicability of the method to pharmacokinetic studies of nalidixic acid in humans is demonstrated and the limit of sensitivity is lower than 0.5 micrograms/ml of plasma or urine for each compound. Expand
The effect of the 4-quinolone enoxacin on plasma theophylline concentrations
It is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylla, and concomitant use of both drugs is necessary, to avoid toxicity. Expand