Pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans

✍ Scribed by Tom B. Vree; Magdalena Van Den Biggelaar-Martea; Corrien P. W. G. M. Verwey-Van Wissen; Jeroen B. Vree; Pieter J. M. Guelen

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 558 KB
• Volume: 14
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510140605

✦ Synopsis

The aim of this investigation was to assess the pharmacokinetics of naproxen in 10 human subjects after an oral dose of 500 mg using a direct HPLC analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. The mean t , of naproxen in 9 subjects was 24'756.4 h (range 16 to 36 h). The t , of 7.4 as found in subject number 10 must, therefore, be regarded as an extraordinary case (p<0.0153).

Naproxen acyl glucuronide accounts for 50-8 k 7.32 per cent of the dose, its isomerized conjugate isoglucuronide for 6-5 k 2.0 per cent, O-desmethylnaproxen acyl glucuronide for 14.3k3.4 per cent, and its isoglucuronide for 5.5k 1.3 per cent (n= 10; 100h collection period). Naproxen and Odesmethylnaproxen are excreted in negligible amounts (< 1 per cent). Even though urine pH of the subjects was kept acid (range pH 5-0-5-5) in order to stabilize the acyl glucuronides, isomerization takes place in blood when the acyl glucuronide is released from the liver for excretion by the kidney. Binding to plasma proteins was measured as 98 per cent and 100 per cent, respectively for the unconjugated compounds naproxen and O-desmethylnaproxen. Binding of the acyl glucuronides was less, being 92 per cent; for naproxen acyl glucuronide, 66 per cent for naproxen isoglucuronide, 72 per cent for O-desmethylnaproxen acyl glucuronide and 42 per cent for O-desmethylnaproxen isoglucuronide.