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Absorption and disposition including enterohepatic circulation of ( 14 C) roquinimex after oral administration to healthy volunteers
Author(s) -
Strandgården Kerstin,
Höglund Peter,
Grönquist Lena,
Svensson Leif,
Olov Gunnarsson Per
Publication year - 2000
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/1099-081x(200003)21:2<53::aid-bdd214>3.0.co;2-f
Subject(s) - enterohepatic circulation , pharmacokinetics , chemistry , urine , high performance liquid chromatography , oral administration , chromatography , absorption (acoustics) , metabolite , bioavailability , pharmacology , feces , hydroxylation , metabolism , biochemistry , medicine , biology , paleontology , physics , acoustics , enzyme
The absorption and disposition of roquinimex (Linomide®) were studied in four male and two female healthy volunteers. The subjects received a single oral aqueous solution of 14 C‐labelled roquinimex, about 0.1 mg/kg, after an overnight fast. Blood samples were taken and urine and faeces were collected for 10 days after dosing. The plasma, urine and faeces concentrations of roquinimex and metabolites were determined by high‐performance liquid chromatography (HPLC) with radiochemical detection. The metabolites were identified by HPLC–mass spectroscopy (MS). The plasma concentration–time profiles of roquinimex exhibited a rapid absorption followed by a bi‐exponential disposition. A secondary peak was observed between 6 and 8 h, indicating enterohepatic circulation (EHC) of roquinimex. The terminal disposition half‐life was estimated as 27 h. The primary metabolic pathways of roquinimex were hydroxylation, demethylation and conjugation. The major compound in plasma was roquinimex; metabolites were only occasionally detected. In urine and faeces, roquinimex accounted for 2% of the dose and conjugated and hydroxylated metabolites each accounted for about 30% of the dose. A model was derived for the plasma concentrations of roquinimex and the amount of urinary excreted roquinimex to take into account EHC. This model improved the goodness‐of‐fit according to common goodness‐of‐fit criteria. The values of the pharmacokinetic parameters were similar using compartmental and non‐compartmental methods, indicating that the contribution of EHC of roquinimex is of minor importance in the evaluation of the pharmacokinetics of roquinimex. Copyright © 2000 John Wiley & Sons, Ltd.