Pharmacokinetics of nalidixic acid in man: hydroxylation and glucuronidation.
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.
Vree
T B
TB
Department of Clinical Pharmacy, St. Radboud Hospital, Nijmegen, the Netherlands.
Wijnands
W J
WJ
Baars
A M
AM
Hekster
Y A
YA
D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009268:Nalidixic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D011485:Protein Binding
C025188:7-carboxynalidixic acid; C012368:7-hydroxynalidixic acid; D009268:Nalidixic Acid; D005966:Glucuronidase