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Nonlinear plasma level response to high doses of naproxen
Author(s) -
Runkel Richard,
Forchielli Enrico,
Sevelius Hilli,
Chaplin Melvin,
Segre Eugene
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974153261
Subject(s) - naproxen , chemistry , oral dose , absorption (acoustics) , pharmacokinetics , plasma levels , plasma clearance , medicine , endocrinology , plateau (mathematics) , plasma concentration , mathematics , materials science , mathematical analysis , alternative medicine , pathology , composite material
The plasma level curves of oral doses of naproxen ranging from 125 to 900 mg were studied in normal sub;ects. Areas under plasma concentration vs time curves increased linearly with dose incmments up to 500 mg twice a day, but larger doses resulted in a plateau effect. Experiments with tritium‐labeled naproxen showed that there was no difference in the fraction of drug excreted in the stools whether the dose was 250 or 900 mg, eliminating incomplete absorption as a factor. Accelerated renal clearance at high doses because of disproportionate increases in the amount of unbound drug appeared to be the most likely explanation for the plateau effect.