ISSN:
1573-904X
Keywords:
prinomide tromethamine pharmacokinetics
;
Langmuir-type protein binding
;
competitive cobinding
;
in vivo metabolite–protein interaction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and its metabolite were dose proportional. The nonlinear pharmacokinetic behavior of total prinomide and p-hydroxy metabolite was found to be caused by both saturable and mutually dependent competitive Langmuir-type plasma protein binding between prinomide and its p-hydroxy metabolite. The extent of the protein interaction displayed at steady state was due to the extensive accumulation of the p-hydroxy metabolite. While ligand–protein interactions are known for xenobiotic competitors, the characteristic behavior of prinomide is the first known example to be reported for a competitive protein interaction between a xenobiotic and its own in vivo generated metabolite. The findings of this study may have implications regarding the disposition of other extensively bound nonsteroidal antiinflammatory drugs with long-lived metabolites.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018916811904
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