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Absorption and excretion of tolmetin in arthritic patients
Author(s) -
Grindel Joseph M.,
Migdalof Bruce H.,
Plostnieks Janis
Publication year - 1979
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/cpt1979261122
Subject(s) - excretion , absorption (acoustics) , pharmacology , medicine , chemistry , materials science , composite material
The absorption, kinetics, biotransformation, and excretion of tolmetin and its metabolites were studied in patients with rheumatoid arthritis (RA) to evaluate the effects of the disease on tolmetin disposition. Five RA patients were stabilized on tolmetin sodium (300 mg, 4 times daily for 14 days) before receiving a single oral solution dose of tolmetin‐ 14 C sodium (300 mg as the acid) on day 15. Tolmetin was rapidly and completely absorbed (peak time, 20 to 60 min) and eliminated rapidly from plasma with a biphasic decay curve (t½β ≅ 2.1 hr). MCPA, the oxidative metabolite, appeared more slowly (peak time, 40 to 90 min) but was eliminated rapidly in a biphasic manner (t½β ≅ 1.7 hr). The terminal elimination phases for both tolmetin and MCPA demonstrated a curvature which suggested possible nonlinearity in the kinetic disposition of the drug. There were no apparent effects of the disease on the kinetics of tolmetin or MCPA. Tolmetin, MCPA, and tolmetin glucuronide were recovered quantitatively in urine (0 to 72 hr) with most of the excretion occurring in the 0‐ to 24‐hr period. A significant increase, relative to data on normal subjects, in the renal clearance of both tolmetin and MCPA was noted. Concomitant increase in the apparent volume of distribution secondary to reported decreases in the plasma protein binding of tolmetin appeared to be the reason for increased renal clearance of tolmetin.